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The Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo and Best Supportive Care in Subjects With Red Blood Cell (RBC) Transfusion-Dependent Anemia and Thrombocytopenia Due to International Prognostic Scoring System (IPSS) Low Risk Myelodysplastic Syndrome (MDS)

Primary Purpose

Myelodysplastic Syndrome

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Oral Azacitidine

Placebo

Best Supportiv Care (BSC)

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

18 years or older
Have a documented diagnosis of MDS
Anemia that requires red blood cell transfusions
Thrombocytopenia (sustained for at least 21 days) within 14 days prior to randomization
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Must agree to follow pregnancy precautions as required by protocol.
Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted

Exclusion Criteria:

Secondary or hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy
Prior treatment with azacitidine, decitabine, other hypomethylating agents and lenalidomide (for lenalidomide : unless the last dose received is >= 8 weeks prior to inclusion into the study).
Prior allogeneic or autologous stem cell transplant
Eligible for allogenic or autologous stem cell transplant
History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect
Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s), or microvascular disorder(s)
Use of cytotoxic, chemotherapeutic, targeted or investigational agents/therapies, thrombopoiesis-stimulating agents (TSAs), erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, and within 28 days prior to randomization
Ongoing medically significant adverse events from previous treatment, regardless of the time period
Concurrent use of iron-chelating agents, (except for subjects on a stable or decreasing dose for at least 8 weeks (56 days) prior to randomization), corticosteroid (except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS)
Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 3 years. (Basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, and incidental histologic finding of prostate cancer) (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system is allowed)
Significant active cardiac disease within the previous 6 months
Uncontrolled systemic fungal, bacterial, or viral infection
Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence of active Hepatitis B Virus (HBV) infection
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
Abnormal coagulation parameters
Abnormal liver function test results
Abnormal kidney function test results
Known or suspected hypersensitivity to azacitidine or mannitol
Any significant medical condition, laboratory abnormality, or psychiatric illness

Sites / Locations

Alta Bates Comprehensive Cancer Center
Tower Hematology/Oncology Medical Group and Tower Cancer Research Found
City Of Hope
California Cancer Associates for Research and Excellence cCARE
Marin Oncology Associates
UCSD-Thornton Hospital
University of Southern California Norris Cancer Center
Yale Cancer Center
University of Florida Health Cancer Center at Orlando Health
Phoebe Cancer Center of Phoebe Putney Memorial Hospital
Robert H Lurie Comprehensive Cancer Center NW Univ
University Of Illinois At Chicago
University Of Chicago Medical Center
Loyola University Chicago
University Of Kansas Medical Center
University of Louisville, J.G. Brown Cancer Center
Hematology And Oncology Specialists, Llc
Johns Hopkins Medicine
UMASS Memorial Hospital
Mayo Clinic
Jackson Oncology Associates PLLC
Saint Luke's Cancer Institute
Kansas City VA Medical Center University of Kansas Medical Center
University Of Nebraska Medical Center
Weill Cornell Medical College - New York - Presbyterian Hospital
Icahn School of Medicine at Mount Sinai Medical Center
Levine Cancer Institute
Eastern Institute of Medical Sciences
University Hospitals of Cleveland Case Medical Center
Ohio State University Medical Center
Kaiser Permanente Northwest Oncology Hematology
University Of Pennsylvania
Western Pennsylvania Cancer Institute
Brooke Army Medical Center Francis Street Medical Center
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Michael Debakey VA Medical Center
Millennium Physicians - Oncology
VA Commonwealth University - Massey Cancer Center
Fred Hutchinson.Cancer Center
Waukesha Memorial Hospital
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Oral Azacitidine

Placebo

Arm Description

Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle.

Arm 2: Identically matching placebo tablets plus best supportive care on days 1 to 21 of each 28-day treatment cycle.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days

RBC transfusion (tfx) independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 56 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 56 days (i.e., day 1 to day 56, day 2 to day 57) were considered as a 56-day RBC transfusion independent responder.

Secondary Outcome Measures

Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days

Duration of RBC transfusion independence was analyzed only for participants who achieved RBC transfusion independence of ≥ 56 days on treatment. Duration of RBC transfusion independence was defined as the time from the date transfusion independence is first observed (day 1 of a ≥ 56 days period without a transfusion) until the date the participants had a subsequently documented RBC transfusion. In the event a participant had more than one ≥56 days rolling periods which met the RBC independence criteria, the duration with the longest rolling period was used in the analysis. Participants who maintained RBC TI through the end of the treatment period were censored at the date of treatment discontinuation, death, or 1 day before the start of the subsequent MDS treatment (if any), whichever occurred first, or the particiapnts latest available assessment date in the database if the treatment was still on-going.

Time to RBC Transfusion Independence for at Least 56 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days

Time to RBC transfusion independence of ≥ 56 days was defined as the time between randomization and the date onset of transfusion independence was first observed (ie, Day 1 of 56 without any RBC transfusions).

Duration of RBC Transfusion Reduction for Participants Who Achieved RBC Transfusion Reduction of at Least 4 Units of RBCs for at Least 8 Weeks

A participant was considered as a RBC transfusion reduction responder if the participant had at least 4 units reduction in transfusion units over any consecutive 56 days period compared to the baseline transfusion units in 56 days.

Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence for ≥ 84 Days

RBC transfusion independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 84 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 84 days (i.e., day 1 to day 84, day 2 to day 85) were considered as a 84-day RBC transfusion independent responder.

Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days

Duration of RBC transfusion independence was analyzed only for participants who achieved RBC transfusion independence of ≥ 84 days on treatment. Duration of RBC transfusion independence was defined as the time from the date transfusion independence is first observed (day 1 of a ≥ 84 days period without a transfusion) until the date the participants had a subsequently documented RBC transfusion. In case a participant had more than one ≥84 days rolling periods which met the RBC independence criteria, the duration with the longest rolling period was used in the analysis.

Time to RBC Transfusion Independence for at Least 84 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days

Time to RBC transfusion independence of ≥ 84 days was defined as the time between randomization and the date onset of transfusion independence was first observed (ie, Day 1 of 84 without any RBC transfusions).

Percentage of Participants With an Erythroid Hematological Improvement (HI-E) Response According to 2006 IWG Criteria

Erythroid HI-E improvement was defined as a hemoglobin increase of ≥ 1.5 g/dL; or a reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a hemoglobin of ≤ 9.0 g/dL on treatment were counted in the RBC transfusion response evaluation.

Percentage of Participants With a Hematological Improvement Response in Platelets (HI-P) According to 2006 IWG Criteria

HI-P response was defined according to IWG 2006 criteria (Cheson, 2006) and as: 1. Absolute increase of ≥ 30 X 10^9/L for participants^ starting with > 20 X 10^9/L platelets; 2. Increase from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%. HI-P must have lasted at least 8 weeks.

Percentage of Participants Who Achieved Platelet Transfusion Independence With a Duration of ≥ 8 Weeks (56 Days)

Platelet transfusion independence was defined as the absence of any platelet transfusion during any consecutive "rolling" 56 days during the treatment period, (ie, Day 1 to 56, Day 2 to 57, Days 3 to 58, etc.). Participants were considered platelet transfusion dependent at baseline if they had received ≥ 2 platelet transfusions during the 56 days immediately preceding randomization and had no consecutive 28-day period during which no platelet transfusions were administered.

Time to Platelet Transfusion Independence

Time to platelet transfusion independence was defined as the time between randomization and the first documented date of onset of transfusion independence (ie, Day 1 of 56 without any platelet transfusions).

Kaplan-Meier Estimate of Overall Survival (OS)

Overall survial was defined as the time from randomization to death from any cause, and was calculated using randomization date and date of death, or date of last follow-up for censored participants. All subjects were followed until drop out (withdrawal of consent from further data collection or lost to follow-up), death, or study closure. Participants who dropped out or were alive at study closure (or at the time of the interim analysis) had their OS times censored at the time of last contact, as appropriate. Overall survival was assessed as an interim analysis at the time of the primary analysis.

Percentage of Participants With a Hematologic Response According to the 2006 IWG Criteria for MDS

Hematologic response was defined as: A complete response (CR): <5% myeloblasts, and normal maturation of all cell lines; Peripheral blood (PB) shows: hemoglobin >10 g/dL, neutrophils ≥1.0x10^9/L, platelets ≥100x10^9/dL, blasts (0%) Partial Response (PR): same as CR bone marrow (BM) shows blasts decreased by ≥ 50% over pre-treatment but still > 5%; Cellularity and morphology not relevant Marrow CR: BM: ≤ 5% myeloblasts and decrease by ≥ 50% over pre-treatment PB Stable disease (SD): failure to achieve at least PR, but no evidence of progression for > 8 wks Failure: death during treatment or disease progression Disease Progression for those with: Less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts 5%-10% blasts:≥ 50% increase to > 10% blasts 10%-20% blasts:≥ 50% increase to > 20% blasts 20%-30% blasts ≥ 50% increase to > 30% blasts Any of the following: ≥ 50% decrease from maximum remission/response in granulocytes or platelets

Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)

Participants with a documented diagnosis of AML arising from previous MDS documented diagnosis.

Time to Progression to Acute Myeloid Leukemia (AML) Among Participants Who Progressed to AML

Time to AML progression was defined as the time from the date of randomization until the date the subject has documented progression to AML. For participants who had progression to AML documented in MLL central lab report, the earliest sample collection date with the diagnosis of "s-AML arising from previous MDS" was used as the date to AML progression.

Percentage of Participants With Significant Bleeding Events

Clinically significant bleeding event was defined as: any intracranial or retroperitoneal bleed; bleeding requiring transfusions of > 2 units of blood/blood products; bleeding associated with a decrease in hemoglobin of > 2 g/dL; or bleeding from any site requiring transfusions of > 2 units of blood.

Number of Participants With Treatment Emergent Adverse Events (TEAE)

A TEAE was defined as an adverse event that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug. A serious adverse event (SAE) is any: Death; Life-threatening event; Any inpatient hospitalization or prolongation of existing hospitalization; Persistent or significant disability or incapacity; Congenital anomaly or birth defect; Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.

Mean Change From Baseline in the Physical Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Cycle 6

The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.

Mean Change From Baseline in the Social Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6

Mean Change From Baseline in the Emotional Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6

Mean Change From Baseline in the Functional Well-Being Component of the FACT-An Instrument at Cycle 6

Mean Change From Baseline in the Anemia Subscale Within FACT-An Instrument at Cycle 6

Mean Change From Baseline in the Fatigue-Related Subscale Within the FACT-An Instrument at Cycle 6

Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index (FACT-An TOI) Summary Scale Within the FACT-An Instrument at Cycle 6

The FACT-G and FACT-An score are summed to form the FACT-An total score. The FACT-An Trial Outcome Index (TOI) consists of the summation of a "summary scale" and includes the Physical Well-being, (PWB; 7 items; score range, 0-28), the Functional Well-being (7 items; score range, 0-28) and the Anemia subscale consisting of 20 items on the same five-point scale, with 13 of them measuring fatigue related symptoms (FS) and seven measuring non-FS. The FACT-An TOI has been demonstrated to be a sensitive indicator of clinical outcomes in a number of diseases including MDS. The Fact-TOI score ranges from 0 to 136. Higher scores on all scales of the Fact-An and subscales on the FACT-TOI reflect better quality of life or fewer symptoms.

Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General (FACT-G) Summary Scale Within the FACT-An Instrument at Cycle 6

The FACT-An is a 47-item, cancer-specific questionnaire consisting of a core 27-item general questionnaire (i.e., the Functional Assessment of Cancer Therapy-General [FACT-G]) The FACT-G measures the 4 domains on a 5-point scale ranging from 0 (not at all) to 4 (very much). The 4 domains are: Physical Well-being (PWB; 7 items; score range, 0-28), Social/Family Well-being (SWB; 7 items; score range, 0-28), Emotional Well-being (EWB; 6 items; score range, 0-24), and Functional Well-being (7 items; score range, 0-28). The FACT-G is a summation composed of a "summary scale" including the PWB, SWB, EWB and FWB. The FACT-G score range is from 0 to 108. For all summary scales including FACT-G, a higher score indicates better HRQoL or lower level of symptoms.

Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-Total Score at Cycle 6

The FACT-G and the anemia subscale (AnS) are summed to form the FACT-An total score and the total score ranges from 0 to 188. The FACT-G measures the 4 domains on a 5-point scale ranging from 0 (not at all) to 4 (very much). The 4 domains are: Physical Well-being (PWB; 7 items; score range, 0-28), Social/Family Well-being (SWB; 7 items; score range, 0-28), Emotional Well-being (EWB; 6 items; score range, 0-24), and Functional Well-being (7 items; score range, 0-28). The AnS consists of 20 items on the same 5-point scale, with 13 of them measuring fatigue-related symptoms (FS) and 7 measuring non-FS. The AnS and FS scores can range from 0-80 and 0-52, respectively. For all domains and summary subscales, a higher score indicates better HRQoL or lower level of symptoms.

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Physical Well-Being Domain Within the FACT-An Instrument at Cycle 6

A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Social Well-Being Domain Within the FACT-An Instrument at Cycle 6

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Emotional Well-Being Domain Within the FACT-An Instrument at Cycle 6

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Functional Well-Being Domain Within the FACT-An Instrument at Cycle 6

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Anemia Subscale Domain Within the FACT-An Instrument at Cycle 6

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Fatigue Related Symptoms Subscale Domain Within the FACT-An Instrument at Cycle 6

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index Subscale Domain Within the FACT-An Instrument at Cycle 6

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General Subscale Domain Within the FACT-An Instrument at Cycle 6

Percentage of Participants With a Clinically Meaningful Improvement (CMI) From Baseline in the Functional Assessment of Cancer Therapy Anemia-Total Score Domain Within the FACT-An Instrument at Cycle 6

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by ≥2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level (EQ-5D-3L) Mobility Dimension Responses at Cycle 6

The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by ≥1 level], no change, worsened [by ≥1 level], and missing) from baseline are reported.

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level of Self-Care Dimension Responses at Cycle 6

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level Usual Activities Dimension Responses at Cycle 6

TThe EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by ≥1 level], no change, worsened [by ≥1 level], and missing) from baseline are reported.

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Pain/Discomfort Dimension Responses at Cycle 6

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Anxiety/Depression Dimension Responses at Cycle 6

Healthcare Resource Utilization (HRU): Number of Participants Who Were Hospitalized During the Treatment Period

The number of reasons for hospitalizations and hospital admissions during the treatment period were monitored and include those associated with: AEs, protocol-driven procedures, transfusions, non-protocol procedures, elective procedures or those associated with social, practical or technical reasons in the absence of AEs. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.

Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Due to Any Reason During the Treatment Period

The total number of days hospitalized due to any reason during the treatment period was monitored. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.

Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Per Total Patient-Years

The number of days hospitalized per total patient years. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.

Full Information

NCT ID

NCT01566695

First Posted

March 27, 2012

Last Updated

September 27, 2023

Sponsor

Celgene

1. Study Identification

Unique Protocol Identification Number

NCT01566695

Brief Title

The Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo and Best Supportive Care in Subjects With Red Blood Cell (RBC) Transfusion-Dependent Anemia and Thrombocytopenia Due to International Prognostic Scoring System (IPSS) Low Risk Myelodysplastic Syndrome (MDS)

Official Title

A Phase 3, Multicenter, Randomized, Double-blind Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Subjects With Red Blood Cell Transfusion-dependent Anemia and Thrombocytopenia Due to IPSS Lower-risk Myelodysplastic Syndromes.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

April 26, 2013 (Actual)

Primary Completion Date

January 25, 2019 (Actual)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celgene

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Evaluation of the Efficacy and Safety of Oral Azacitidine plus Best Supportive care versus Placebo and Best Supportive care in subjects with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia due to International Prognostic Scoring System (IPSS) lower risk myelodysplastic syndromes (MDS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myelodysplastic Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

216 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Oral Azacitidine

Arm Type

Experimental

Arm Description

Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Arm 2: Identically matching placebo tablets plus best supportive care on days 1 to 21 of each 28-day treatment cycle.

Intervention Type

Drug

Intervention Name(s)

Oral Azacitidine

Other Intervention Name(s)

CC-486

Intervention Description

300 mg daily, days 1 to 21 of each 28-day treatment cycle

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Identically matching placebo tablets on day 1 to 21 of each 28-day treatment cycle.

Intervention Type

Other

Intervention Name(s)

Best Supportiv Care (BSC)

Intervention Description

BSC included and was not limited to packed RBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.

Primary Outcome Measure Information:

Title

Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days

Description

Time Frame

Each participant was assessed for at least 56 days or more; from the date of randomization of study drug up to the data cut-off date of 25 January 2019, approximately 5 months.

Secondary Outcome Measure Information:

Title

Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days

Description

Time Frame

From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo

Title

Time to RBC Transfusion Independence for at Least 56 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days

Description

Time Frame

From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo

Title

Duration of RBC Transfusion Reduction for Participants Who Achieved RBC Transfusion Reduction of at Least 4 Units of RBCs for at Least 8 Weeks

Description

Time Frame

From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo

Title

Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence for ≥ 84 Days

Description

Time Frame

Title

Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days

Description

Time Frame

Title

Time to RBC Transfusion Independence for at Least 84 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days

Description

Time Frame

Title

Percentage of Participants With an Erythroid Hematological Improvement (HI-E) Response According to 2006 IWG Criteria

Description

Time Frame

Title

Percentage of Participants With a Hematological Improvement Response in Platelets (HI-P) According to 2006 IWG Criteria

Description

Time Frame

Title

Percentage of Participants Who Achieved Platelet Transfusion Independence With a Duration of ≥ 8 Weeks (56 Days)

Description

Time Frame

Title

Time to Platelet Transfusion Independence

Description

Time Frame

Title

Kaplan-Meier Estimate of Overall Survival (OS)

Description

Time Frame

From randomization to death from any cause; up to the data cut-off of date of 25 January 2019; maximum follow-up time for all participants was 67.9 months for the oral azacitidine arm and 64.8 months for placebo arm

Title

Percentage of Participants With a Hematologic Response According to the 2006 IWG Criteria for MDS

Description

Time Frame

Response was assessed every 3 cycles; up to the data cut-off date of 25 Jan 2019; median duration of exposure to oral azacitidine was 86.0 days and 119.0 days for placebo

Title

Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)

Description

Participants with a documented diagnosis of AML arising from previous MDS documented diagnosis.

Time Frame

From randomization of study drug to the end up to final data cut-off date of 25 January 2019; maximum follow-up time was 67.9 months for azacitidine and 64.8 months for placebo group

Title

Time to Progression to Acute Myeloid Leukemia (AML) Among Participants Who Progressed to AML

Description

Time Frame

From randomization of study drug to progression of AML; up to final data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo

Title

Percentage of Participants With Significant Bleeding Events

Description

Time Frame

From date of randomization until 28 days after the last dose of IP; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo

Title

Number of Participants With Treatment Emergent Adverse Events (TEAE)

Description

Time Frame

From first dose of IP up to 28 days after the last dose of IP; up to data cut-off date of 25 Jan 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo

Title

Mean Change From Baseline in the Physical Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Mean Change From Baseline in the Social Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Mean Change From Baseline in the Emotional Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Mean Change From Baseline in the Functional Well-Being Component of the FACT-An Instrument at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Mean Change From Baseline in the Anemia Subscale Within FACT-An Instrument at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Mean Change From Baseline in the Fatigue-Related Subscale Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index (FACT-An TOI) Summary Scale Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General (FACT-G) Summary Scale Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-Total Score at Cycle 6

Description

Time Frame

Baseline to Cycle 6 Day 1

Title

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Physical Well-Being Domain Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Cycle 6 Day 1

Title

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Social Well-Being Domain Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Cycle 6 Day 1

Title

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Emotional Well-Being Domain Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Cycle 6 Day 1

Title

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Functional Well-Being Domain Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Cycle 6 Day 1

Title

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Anemia Subscale Domain Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Cycle 6 Day 1

Title

Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Fatigue Related Symptoms Subscale Domain Within the FACT-An Instrument at Cycle 6

Description

Time Frame

Cycle 6 Day 1

Title

Description

Time Frame

Cycle 6 Day 1

Title

Description

Time Frame

Cycle 6 Day 1

Title

Description

Time Frame

Cycle 6 Day 1

Title

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

Description

Time Frame

From Baseline to Cycle 2 Day 1 (C2D1)

Title

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

Description

Time Frame

From Baseline to Cycle 3 Day 1 (C3D1)

Title

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

Description

Time Frame

From Baseline to Cycle 4 Day 1 (C4D1)

Title

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

Description

Time Frame

From Baseline to Cycle 5 Day 1 (C5D1)

Title

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

Description

Time Frame

From Baseline to Cycle 6 Day 1 (C6 D1)

Title

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

Description

Time Frame

From Baseline to Cycle 7 Day 1 (C7D1)

Title

Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5

Description

Time Frame

From Baseline to End of Treatment

Title

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level (EQ-5D-3L) Mobility Dimension Responses at Cycle 6

Description

Time Frame

From Baseline to Cycle 6 Day 1

Title

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level of Self-Care Dimension Responses at Cycle 6

Description

Time Frame

From Baseline to Cycle 6 Day 1

Title

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level Usual Activities Dimension Responses at Cycle 6

Description

Time Frame

From Baseline to Cycle 6 Day 1

Title

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Pain/Discomfort Dimension Responses at Cycle 6

Description

Time Frame

From Baseline to Cycle 6 Day 1

Title

Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Anxiety/Depression Dimension Responses at Cycle 6

Description

Time Frame

From Baseline to Cycle 6 Day 1

Title

Healthcare Resource Utilization (HRU): Number of Participants Who Were Hospitalized During the Treatment Period

Description

Time Frame

From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo

Title

Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Due to Any Reason During the Treatment Period

Description

Time Frame

Title

Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Per Total Patient-Years

Description

The number of days hospitalized per total patient years. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 18 years or older Have a documented diagnosis of MDS Anemia that requires red blood cell transfusions Thrombocytopenia (sustained for at least 21 days) within 14 days prior to randomization Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Must agree to follow pregnancy precautions as required by protocol. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted Exclusion Criteria: Secondary or hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy Prior treatment with azacitidine, decitabine, other hypomethylating agents and lenalidomide (for lenalidomide : unless the last dose received is >= 8 weeks prior to inclusion into the study). Prior allogeneic or autologous stem cell transplant Eligible for allogenic or autologous stem cell transplant History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s), or microvascular disorder(s) Use of cytotoxic, chemotherapeutic, targeted or investigational agents/therapies, thrombopoiesis-stimulating agents (TSAs), erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, and within 28 days prior to randomization Ongoing medically significant adverse events from previous treatment, regardless of the time period Concurrent use of iron-chelating agents, (except for subjects on a stable or decreasing dose for at least 8 weeks (56 days) prior to randomization), corticosteroid (except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS) Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 3 years. (Basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, and incidental histologic finding of prostate cancer) (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system is allowed) Significant active cardiac disease within the previous 6 months Uncontrolled systemic fungal, bacterial, or viral infection Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence of active Hepatitis B Virus (HBV) infection Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding Abnormal coagulation parameters Abnormal liver function test results Abnormal kidney function test results Known or suspected hypersensitivity to azacitidine or mannitol Any significant medical condition, laboratory abnormality, or psychiatric illness

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Alta Bates Comprehensive Cancer Center

City

Berkeley

State/Province

California

ZIP/Postal Code

94704

Country

United States

Facility Name

Tower Hematology/Oncology Medical Group and Tower Cancer Research Found

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

Facility Name

City Of Hope

City

Duarte

State/Province

California

ZIP/Postal Code

91010-301

Country

United States

Facility Name

California Cancer Associates for Research and Excellence cCARE

City

Escondido

State/Province

California

ZIP/Postal Code

92025

Country

United States

Facility Name

Marin Oncology Associates

City

Greenbrae

State/Province

California

ZIP/Postal Code

94904-2007

Country

United States

Facility Name

UCSD-Thornton Hospital

City

La Jolla

State/Province

California

ZIP/Postal Code

92093-0943

Country

United States

Facility Name

University of Southern California Norris Cancer Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90033

Country

United States

Facility Name

Yale Cancer Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

Facility Name

University of Florida Health Cancer Center at Orlando Health

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Phoebe Cancer Center of Phoebe Putney Memorial Hospital

City

Albany

State/Province

Georgia

ZIP/Postal Code

31701

Country

United States

Facility Name

Robert H Lurie Comprehensive Cancer Center NW Univ

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

University Of Illinois At Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

University Of Chicago Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Loyola University Chicago

City

Maywood

State/Province

Illinois

ZIP/Postal Code

60153

Country

United States

Facility Name

University Of Kansas Medical Center

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66160-7233

Country

United States

Facility Name

University of Louisville, J.G. Brown Cancer Center

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Hematology And Oncology Specialists, Llc

City

Metairie

State/Province

Louisiana

ZIP/Postal Code

70006

Country

United States

Facility Name

Johns Hopkins Medicine

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231

Country

United States

Facility Name

UMASS Memorial Hospital

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01655

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Jackson Oncology Associates PLLC

City

Jackson

State/Province

Mississippi

ZIP/Postal Code

39202

Country

United States

Facility Name

Saint Luke's Cancer Institute

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64111

Country

United States

Facility Name

Kansas City VA Medical Center University of Kansas Medical Center

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64128

Country

United States

Facility Name

University Of Nebraska Medical Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198-6805

Country

United States

Facility Name

Weill Cornell Medical College - New York - Presbyterian Hospital

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

Icahn School of Medicine at Mount Sinai Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Levine Cancer Institute

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

Eastern Institute of Medical Sciences

City

Greenville

State/Province

North Carolina

ZIP/Postal Code

27834

Country

United States

Facility Name

University Hospitals of Cleveland Case Medical Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106-5000

Country

United States

Facility Name

Ohio State University Medical Center

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

Kaiser Permanente Northwest Oncology Hematology

City

Portland

State/Province

Oregon

ZIP/Postal Code

97227

Country

United States

Facility Name

University Of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Western Pennsylvania Cancer Institute

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

Facility Name

Brooke Army Medical Center Francis Street Medical Center

City

Fort Sam Houston

State/Province

Texas

ZIP/Postal Code

78235-8200

Country

United States

Facility Name

Local Institution - 900

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Michael Debakey VA Medical Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Millennium Physicians - Oncology

City

Houston

State/Province

Texas

ZIP/Postal Code

77090

Country

United States

Facility Name

VA Commonwealth University - Massey Cancer Center

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298-0037

Country

United States

Facility Name

Fred Hutchinson.Cancer Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109-4417

Country

United States

Facility Name

Waukesha Memorial Hospital

City

Waukesha

State/Province

Wisconsin

ZIP/Postal Code

53188-5099

Country

United States

Facility Name

Local Institution - 137

City

Garran

State/Province

Australian Capital Territory

ZIP/Postal Code

2605

Country

Australia

Facility Name

Local Institution - 129

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

SA 5000

Country

Australia

Facility Name

Local Institution - 134

City

Clayton

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

Facility Name

Local Institution - 132

City

Frankston

State/Province

Victoria

ZIP/Postal Code

3199

Country

Australia

Facility Name

Local Institution - 131

City

Camperdown

ZIP/Postal Code

2050

Country

Australia

Facility Name

Local Institution - 127

City

Epping, VIC

ZIP/Postal Code

3076

Country

Australia

Facility Name

Local Institution - 133

City

Fitzroy

ZIP/Postal Code

3065

Country

Australia

Facility Name

Local Institution - 135

City

Kogarah

ZIP/Postal Code

2217

Country

Australia

Facility Name

Local Institution - 130

City

Malvern

ZIP/Postal Code

3144

Country

Australia

Facility Name

Local Institution - 126

City

Milton, Brisbane

ZIP/Postal Code

4064

Country

Australia

Facility Name

Local Institution - 138

City

Waratah

ZIP/Postal Code

NSW

Country

Australia

Facility Name

Local Institution - 136

City

Woolloongabba

ZIP/Postal Code

QLD 4102

Country

Australia

Facility Name

Local Institution - 203

City

Brasschaat

ZIP/Postal Code

2930

Country

Belgium

Facility Name

Local Institution - 200

City

Brugge

ZIP/Postal Code

8000

Country

Belgium

Facility Name

Local Institution - 202

City

Charleroi

ZIP/Postal Code

6000

Country

Belgium

Facility Name

Local Institution - 201

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Local Institution - 154

City

Fortaleza

State/Province

Ceará

ZIP/Postal Code

60430370

Country

Brazil

Facility Name

Local Institution - 155

City

Curitiba

State/Province

Paraná

ZIP/Postal Code

81520-060

Country

Brazil

Facility Name

Local Institution - 152

City

Porto Alegre

State/Province

Rio Grande Do Sul

ZIP/Postal Code

90035-903

Country

Brazil

Facility Name

Local Institution - 153

City

Rio De Janeiro

ZIP/Postal Code

20231-130

Country

Brazil

Facility Name

Local Institution - 151

City

Sao Paulo

ZIP/Postal Code

05651-901

Country

Brazil

Facility Name

Local Institution - 182

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 2B7

Country

Canada

Facility Name

Local Institution - 178

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 1M9

Country

Canada

Facility Name

Local Institution - 183

City

Barrie

State/Province

Ontario

ZIP/Postal Code

LYM6M2

Country

Canada

Facility Name

Local Institution - 180

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8V 5C2

Country

Canada

Facility Name

Local Institution - 179

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4N 3M5

Country

Canada

Facility Name

Local Institution - 176

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

Facility Name

Local Institution - 181

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2W 1S6

Country

Canada

Facility Name

Local Institution - 177

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H4J 1C5

Country

Canada

Facility Name

Local Institution - 226

City

Brno

State/Province

Jihomoravský Kraj

ZIP/Postal Code

625 00

Country

Czechia

Facility Name

Local Institution - 230

City

Hradec Králové

ZIP/Postal Code

500 05

Country

Czechia

Facility Name

Local Institution - 229

City

Olomouc

ZIP/Postal Code

77520

Country

Czechia

Facility Name

Local Institution - 228

City

Praha

ZIP/Postal Code

128 08

Country

Czechia

Facility Name

Local Institution - 227

City

Praha

ZIP/Postal Code

128 20

Country

Czechia

Facility Name

Local Institution - 253

City

Aarhus

ZIP/Postal Code

8000

Country

Denmark

Facility Name

Local Institution - 252

City

Odense C

ZIP/Postal Code

5000

Country

Denmark

Facility Name

Local Institution - 251

City

Roskilde

ZIP/Postal Code

DK-4000

Country

Denmark

Facility Name

Local Institution - 276

City

Helsinki

ZIP/Postal Code

00029 HUS

Country

Finland

Facility Name

Local Institution - 277

City

Turku

ZIP/Postal Code

20521

Country

Finland

Facility Name

Local Institution - 305

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Local Institution - 304

City

Marseille Cedex 9

ZIP/Postal Code

13009

Country

France

Facility Name

Local Institution - 301

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

Local Institution - 308

City

Paris

ZIP/Postal Code

7575

Country

France

Facility Name

Local Institution - 307

City

Pierre-Bénite Cedex

ZIP/Postal Code

69495

Country

France

Facility Name

Local Institution - 302

City

Rennes Cedex

ZIP/Postal Code

35033

Country

France

Facility Name

Local Institution - 303

City

Rouen Cedex

ZIP/Postal Code

76038

Country

France

Facility Name

Local Institution - 306

City

Strasbourg

ZIP/Postal Code

67091

Country

France

Facility Name

Local Institution - 300

City

Toulouse Cedex 9

ZIP/Postal Code

31059

Country

France

Facility Name

Local Institution - 309

City

Tours

ZIP/Postal Code

37044

Country

France

Facility Name

Local Institution - 350

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Local Institution - 361

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Local Institution - 359

City

Duesseldorf

ZIP/Postal Code

40479

Country

Germany

Facility Name

Local Institution - 355

City

Dusseldorf

ZIP/Postal Code

40225

Country

Germany

Facility Name

Local Institution - 356

City

Hamburg

ZIP/Postal Code

D-20099

Country

Germany

Facility Name

Local Institution - 353

City

Keil

ZIP/Postal Code

24105

Country

Germany

Facility Name

Local Institution - 351

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Local Institution - 352

City

München

ZIP/Postal Code

81675

Country

Germany

Facility Name

Local Institution - 357

City

Tubingen

ZIP/Postal Code

72076

Country

Germany

Facility Name

Local Institution - 360

City

Ulm

ZIP/Postal Code

89081

Country

Germany

Facility Name

Local Institution - 853

City

Heraklion

State/Province

Irakleio

ZIP/Postal Code

71110

Country

Greece

Facility Name

Local Institution - 851

City

Alexandroupolis

ZIP/Postal Code

68100

Country

Greece

Facility Name

Local Institution - 852

City

Athens

ZIP/Postal Code

10676

Country

Greece

Facility Name

Local Institution - 855

City

Athens

ZIP/Postal Code

115 27

Country

Greece

Facility Name

Local Institution - 850

City

Athens

ZIP/Postal Code

124 62

Country

Greece

Facility Name

Local Institution - 854

City

Patras

ZIP/Postal Code

26500

Country

Greece

Facility Name

Local Institution - 453

City

Haifa

ZIP/Postal Code

31096

Country

Israel

Facility Name

Local Institution - 451

City

Petach Tikva

ZIP/Postal Code

49100

Country

Israel

Facility Name

Local Institution - 454

City

Tel Hashomer

ZIP/Postal Code

52621

Country

Israel

Facility Name

Local Institution - 452

City

Tel-Aviv

ZIP/Postal Code

64239

Country

Israel

Facility Name

Local Institution - 482

City

Alessandria

ZIP/Postal Code

15121

Country

Italy

Facility Name

Local Institution - 492

City

Bari

ZIP/Postal Code

70124

Country

Italy

Facility Name

Local Institution - 489

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Facility Name

Local Institution - 494

City

Cagliari

ZIP/Postal Code

09121

Country

Italy

Facility Name

Local Institution - 486

City

Firenze

ZIP/Postal Code

50129

Country

Italy

Facility Name

Local Institution - 479

City

Lecce

ZIP/Postal Code

73100

Country

Italy

Facility Name

Local Institution - 488

City

Milano

ZIP/Postal Code

20122

Country

Italy

Facility Name

Local Institution - 498

City

Milan

ZIP/Postal Code

20089

Country

Italy

Facility Name

Local Institution - 497

City

Novara

ZIP/Postal Code

28100

Country

Italy

Facility Name

Local Institution - 480

City

Palermo

ZIP/Postal Code

90146

Country

Italy

Facility Name

Local Institution - 495

City

Pavia

ZIP/Postal Code

27100

Country

Italy

Facility Name

Local Institution - 496

City

Pisa

ZIP/Postal Code

56126

Country

Italy

Facility Name

Local Institution - 485

City

Reggio Calabria

ZIP/Postal Code

89133

Country

Italy

Facility Name

Local Institution - 484

City

Rionero in Vulture

ZIP/Postal Code

85028

Country

Italy

Facility Name

Local Institution - 487

City

Roma

ZIP/Postal Code

00133

Country

Italy

Facility Name

Local Institution - 490

City

Roma

ZIP/Postal Code

00161

Country

Italy

Facility Name

Local Institution - 481

City

Roma

ZIP/Postal Code

00168

Country

Italy

Facility Name

Local Institution - 499

City

Terni

ZIP/Postal Code

05100

Country

Italy

Facility Name

Local Institution - 477

City

Torino

ZIP/Postal Code

10126

Country

Italy

Facility Name

Local Institution - 493

City

Torrette Di Ancona

ZIP/Postal Code

60020

Country

Italy

Facility Name

Local Institution - 478

City

Udine

ZIP/Postal Code

33100

Country

Italy

Facility Name

Local Institution - 476

City

Venezia - Mestre

ZIP/Postal Code

30174

Country

Italy

Facility Name

Local Institution - 704

City

Busan

ZIP/Postal Code

614-735

Country

Korea, Republic of

Facility Name

Local Institution - 703

City

Daegu

ZIP/Postal Code

700-721

Country

Korea, Republic of

Facility Name

Local Institution - 701

City

Seoul

ZIP/Postal Code

06591

Country

Korea, Republic of

Facility Name

Local Institution - 702

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Facility Name

Local Institution - 700

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

Facility Name

Local Institution - 830

City

Huixquilucan de Degollado

ZIP/Postal Code

52763

Country

Mexico

Facility Name

Local Institution - 828

City

Monterrey

ZIP/Postal Code

64460

Country

Mexico

Facility Name

Local Institution - 829

City

Monterrey

ZIP/Postal Code

64710

Country

Mexico

Facility Name

Local Institution - 827

City

Tlalpan

ZIP/Postal Code

14080

Country

Mexico

Facility Name

Local Institution - 528

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

Facility Name

Local Institution - 527

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

Facility Name

Local Institution - 526

City

Nijmegen

ZIP/Postal Code

6500 HB

Country

Netherlands

Facility Name

Local Institution - 529

City

Rotterdam

ZIP/Postal Code

3075 EA

Country

Netherlands

Facility Name

Local Institution - 552

City

Førde

ZIP/Postal Code

6807

Country

Norway

Facility Name

Local Institution - 551

City

Oslo

ZIP/Postal Code

N-0027

Country

Norway

Facility Name

Local Institution - 582

City

Bydgoszcz

ZIP/Postal Code

85-168

Country

Poland

Facility Name

Local Institution - 576

City

Gdansk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

Local Institution - 579

City

Krakow

ZIP/Postal Code

31-501

Country

Poland

Facility Name

Local Institution - 581

City

Lodz

ZIP/Postal Code

93-510

Country

Poland

Facility Name

Local Institution - 580

City

Torun

ZIP/Postal Code

87-100

Country

Poland

Facility Name

Local Institution - 583

City

Warszawa

ZIP/Postal Code

02-097

Country

Poland

Facility Name

Local Institution - 577

City

Warszawa

ZIP/Postal Code

02-776

Country

Poland

Facility Name

Local Institution - 578

City

Wroclaw

ZIP/Postal Code

50-367

Country

Poland

Facility Name

Local Institution - 604

City

Beja

ZIP/Postal Code

7801-849

Country

Portugal

Facility Name

Local Institution - 600

City

Coimbra

ZIP/Postal Code

3000-075

Country

Portugal

Facility Name

Local Institution - 601

City

Lisboa

ZIP/Postal Code

1099-023

Country

Portugal

Facility Name

Local Institution - 603

City

Lisboa

ZIP/Postal Code

1150-314

Country

Portugal

Facility Name

Local Institution - 602

City

Porto

ZIP/Postal Code

4200-072

Country

Portugal

Facility Name

Local Institution - 626

City

Badalona (Barcelona)

ZIP/Postal Code

8916

Country

Spain

Facility Name

Local Institution - 635

City

Barcelona

ZIP/Postal Code

08025

Country

Spain

Facility Name

Local Institution - 625

City

Barcelona

ZIP/Postal Code

8035

Country

Spain

Facility Name

Local Institution - 636

City

Granada

ZIP/Postal Code

18014

Country

Spain

Facility Name

Local Institution - 629

City

Madrid

ZIP/Postal Code

28009

Country

Spain

Facility Name

Local Institution - 634

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Local Institution - 631

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Local Institution - 632

City

Malaga

ZIP/Postal Code

29010

Country

Spain

Facility Name

Local Institution - 628

City

Oviedo

ZIP/Postal Code

33006

Country

Spain

Facility Name

Local Institution - 630

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

Local Institution - 627

City

Seville

ZIP/Postal Code

41013

Country

Spain

Facility Name

Local Institution - 633

City

Vitoria-Gasteiz, Álava

ZIP/Postal Code

1009

Country

Spain

Facility Name

Local Institution - 653

City

Goeteborg

ZIP/Postal Code

413 45

Country

Sweden

Facility Name

Local Institution - 652

City

Lund

ZIP/Postal Code

222 41

Country

Sweden

Facility Name

Local Institution - 651

City

Stockholm

ZIP/Postal Code

14186

Country

Sweden

Facility Name

Local Institution - 401

City

Adana

ZIP/Postal Code

01250

Country

Turkey

Facility Name

Local Institution - 405

City

Antalya

ZIP/Postal Code

07100

Country

Turkey

Facility Name

Local Institution - 403

City

Istanbul

ZIP/Postal Code

34098

Country

Turkey

Facility Name

Local Institution - 400

City

Istanbul

ZIP/Postal Code

34390

Country

Turkey

Facility Name

Local Institution - 404

City

Mersin

ZIP/Postal Code

33343

Country

Turkey

Facility Name

Local Institution - 402

City

Trabzon

ZIP/Postal Code

61080

Country

Turkey

Facility Name

Local Institution - 685

City

Oxford

State/Province

Oxfordshire

ZIP/Postal Code

OX3 9DU

Country

United Kingdom

Facility Name

Local Institution - 687

City

Aberdeen

ZIP/Postal Code

AB25 2ZN

Country

United Kingdom

Facility Name

Local Institution - 691

City

Birmingham

ZIP/Postal Code

B9 5SS

Country

United Kingdom

Facility Name

Local Institution - 686

City

Bristol

ZIP/Postal Code

BS2 8ED

Country

United Kingdom

Facility Name

Local Institution - 689

City

Cambridge

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Facility Name

Local Institution - 678

City

Cardiff

ZIP/Postal Code

CF14 4XW

Country

United Kingdom

Facility Name

Local Institution - 688

City

Harrow Middlesex

ZIP/Postal Code

HA1 3UJ

Country

United Kingdom

Facility Name

Local Institution - 692

City

Hull

ZIP/Postal Code

HU16 5JQ

Country

United Kingdom

Facility Name

Local Institution - 677

City

Leicester

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

Facility Name

Local Institution - 683

City

Liverpool

ZIP/Postal Code

L7 8XP

Country

United Kingdom

Facility Name

Local Institution - 676

City

London

ZIP/Postal Code

EC1A 7BE

Country

United Kingdom

Facility Name

Local Institution - 684

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

Local Institution - 679

City

Manchester

ZIP/Postal Code

M13 9WL

Country

United Kingdom

Facility Name

Local Institution - 681

City

Nottingham

ZIP/Postal Code

NG5 1PB

Country

United Kingdom

Facility Name

Local Institution - 690

City

Sutton in Ashfield

ZIP/Postal Code

NG17 4JL

Country

United Kingdom

Facility Name

Local Institution - 680

City

Wolverhampton

ZIP/Postal Code

WV10 0QP

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

27148452

Citation

Garcia-Manero G, Almeida A, Giagounidis A, Platzbecker U, Garcia R, Voso MT, Larsen SR, Valcarcel D, Silverman LR, Skikne B, Santini V. Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia. BMC Hematol. 2016 May 3;16:12. doi: 10.1186/s12878-016-0049-5. eCollection 2016.

Results Reference

background

PubMed Identifier

33764805

Citation

Garcia-Manero G, Santini V, Almeida A, Platzbecker U, Jonasova A, Silverman LR, Falantes J, Reda G, Buccisano F, Fenaux P, Buckstein R, Diez Campelo M, Larsen S, Valcarcel D, Vyas P, Giai V, Oliva EN, Shortt J, Niederwieser D, Mittelman M, Fianchi L, La Torre I, Zhong J, Laille E, Lopes de Menezes D, Skikne B, Beach CL, Giagounidis A. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes. J Clin Oncol. 2021 May 1;39(13):1426-1436. doi: 10.1200/JCO.20.02619. Epub 2021 Mar 25.

Results Reference

derived

Links:

URL

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Description

BMS Clinical Trial Information

URL

https://www.bmsstudyconnect.com/us/en/home.html

Description

BMS Clinical Trial Patient Recruiting

URL

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

Description

FDA Safety Alerts and Recalls

Learn more about this trial

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