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5 Day Versus 7 Day Azacitidine in Lower Risk Myelodysplastic Syndrome

Primary Purpose

Myelodysplastic Syndrome

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Azacitidine

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring myelodysplastic syndrome, azacitidine, dosing schedule

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects must satisfy the following criteria in order to be enrolled in this clinical trial: Patients who have been diagnosed with MDS by the FAB criteria and belong to Low or INT-1 risk by the IPSS classification will be enrolled in this study. For the purpose of analysis, chronic myelomonocytic leukemia (CMML) patients with less than 5% of myeloblasts are also classified by the IPSS risk classification. Secondary or treatment-related MDS is allowed, but recurrent or persistent MDS after stem cell is not applicable. The enrolled patients should have anemia (hemoglobin < 10.0g/dL), transfusion dependence, thrombocytopenia (less than 100×10^9/L), or absolute neutrophil count less than 1.80×10^9/L.
18 years of age or older
Life expectancy of at least 12 months
ECOG performance status 2 or less
Serum creatinine less than 1.5 times the upper limit of normal (ULN) level of the investigating institution
Serum bilirubin less than 2.0 times the upper limit of normal (ULN) level of the investigating institution
AST, ALT, and alkaline phosphatase less than 3 times the upper limit of normal (ULN) level of the investigation institution
Patients who can have informed consent and signed the informed consent form
Male patients who have a female partner of childbearing potential must agree to use two types of effective contraceptive methods during the study and for 30 days following the last dose.
Females of childbearing potential (FCBP) must satisfy the following criteria: must agree to use the contraceptive method (oral contraceptives, injectables, hormonal implants; tubal ligation; intra uterine device; spermicidal contraceptives, the sterilized partner) approved by the physician during azacitidine treatment and for 3 months following the last dose, and must have a negative result of serum pregnancy test that was performed within 72 hours prior to starting study drug therapy.

Exclusion Criteria:

Any coexisting major illness or organ failure
HIV positive, or active hepatitis B or C infection
Uncontrolled acute infection
Uncontrolled hemorrhage
Pregnant or lactating
Known or suspected hypersensitivity to azacitidine
Patients diagnosed with malignant hepatic carcinoma or malignant disease within the past 12 months (except in situ carcinoma without complication, cervical or breast intraepithelial neoplasia, or other local malignant carcinoma that is likely to be treated by surgical removal or radiotherapy)

Sites / Locations

Seoul St. Mary's HospitalRecruiting
Asan Medical CenterRecruiting
Seoul National University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

5-day arm

7-day arm

Arm Description

azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care

azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care

Outcomes

Primary Outcome Measures

Overall response rate by modified IWG 2006 response criteria

Overall response rate is evaluated by assessing the percentage of patients with response (complete remission (CR), partial remission (PR), bone marrow CR, and hematologic improvement), response period, and transfusion requirement. Best response during at least 6 cycles of treatment will be assessed if there is no treatment failure or disease progression within 6 cycles of treatment. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.

Secondary Outcome Measures

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

•Safety and tolerability profile of 5-day azacitidine in comparison with 7-day regimen. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.

Cytogenetic response rate by IWG 2006 response criteria

•Cytogenetic response of of 5-day azacitidine in comparison with 7-day regimen. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.

Full Information

NCT ID

NCT01652781

First Posted

July 11, 2012

Last Updated

November 18, 2015

Sponsor

Seoul St. Mary's Hospital

Collaborators

Celgene Corporation

1. Study Identification

Unique Protocol Identification Number

NCT01652781

Brief Title

5 Day Versus 7 Day Azacitidine in Lower Risk Myelodysplastic Syndrome

Official Title

A Randomized, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of 5-day Azacitidine for Patients With Lower-risk Myelodysplastic Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Unknown status

Study Start Date

March 2012 (undefined)

Primary Completion Date

June 2016 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Seoul St. Mary's Hospital

Collaborators

Celgene Corporation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Approved dosing schedule of azacitidine for myelodysplastic syndrome (MDS) is 75 mg/m^2/day subcutaneous for 7 consecutive days every 28 days, which is based on the data from standard chemotherapy regimen and a Phase I safety clinical trial. Since the optimal dosage of this drug has not been found yet, it remains as a subject of clinical study that needs to be examined. If initial toxicity is minimized by developing dosage/regimen that replaces the standard therapy, it will be possible to provide continuous treatment with increased convenience by patients and treating physicians as well as improvement for safety in elderly patients or those with serious cytopenia. In addition, it is expected to lead to a better response by strictly keeping a treatment schedule. Recent US study showed that 5-day regimen showed similar treatment results, but retrospective data from Spain showed lower response rate in 5-day regimen. Considering the recent circumstances around dosage and schedule of azacitidine in lower risk MDS, a Phase II clinical trial is planned in lower risk MDS patients in order to explore the efficacy in 5-day treatment by comparing prospectively with 7-day standard regimen.

Detailed Description

Using block randomization, subjects of Low or intermediate (INT)-1 patients will be equally allocated to the following two types of regimens. Group A: azacitidine 75mg/m^2 subcutaneously for 7 days every 28 days + best supportive care Group B: azacitidine 75mg/m^2 subcutaneously for 5 days every 28 days + best supportive care The study drug, azacitidine, is provided free of charge by Celgene until disease progression or relapse after response, or intolerable toxicity occurs in clinical study subject, or informed consent is withdrawn. No crossover between arms is allowed. Dose escalation in this study is not allowed; on the contrary, dose reduction or dose delay is possible based on adverse events and hematologic recovery.

6. Conditions and Keywords

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

Myelodysplastic Syndrome

Keywords

myelodysplastic syndrome, azacitidine, dosing schedule

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

92 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

5-day arm

Arm Type

Experimental

Arm Description

azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care

Arm Title

7-day arm

Arm Type

Active Comparator

Arm Description

azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Other Intervention Name(s)

vidaza

Intervention Description

5-day arm: azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care 7-day arm: azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care

Primary Outcome Measure Information:

Title

Overall response rate by modified IWG 2006 response criteria

Description

Time Frame

After 6 cycles of treatment up to 25-49 weeks

Secondary Outcome Measure Information:

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

After each course of treatment up to 25-49 weeks

Title

Cytogenetic response rate by IWG 2006 response criteria

Description

Time Frame

After 6 cycles of treatment up to 25-49 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects must satisfy the following criteria in order to be enrolled in this clinical trial: Patients who have been diagnosed with MDS by the FAB criteria and belong to Low or INT-1 risk by the IPSS classification will be enrolled in this study. For the purpose of analysis, chronic myelomonocytic leukemia (CMML) patients with less than 5% of myeloblasts are also classified by the IPSS risk classification. Secondary or treatment-related MDS is allowed, but recurrent or persistent MDS after stem cell is not applicable. The enrolled patients should have anemia (hemoglobin < 10.0g/dL), transfusion dependence, thrombocytopenia (less than 100×10^9/L), or absolute neutrophil count less than 1.80×10^9/L. 18 years of age or older Life expectancy of at least 12 months ECOG performance status 2 or less Serum creatinine less than 1.5 times the upper limit of normal (ULN) level of the investigating institution Serum bilirubin less than 2.0 times the upper limit of normal (ULN) level of the investigating institution AST, ALT, and alkaline phosphatase less than 3 times the upper limit of normal (ULN) level of the investigation institution Patients who can have informed consent and signed the informed consent form Male patients who have a female partner of childbearing potential must agree to use two types of effective contraceptive methods during the study and for 30 days following the last dose. Females of childbearing potential (FCBP) must satisfy the following criteria: must agree to use the contraceptive method (oral contraceptives, injectables, hormonal implants; tubal ligation; intra uterine device; spermicidal contraceptives, the sterilized partner) approved by the physician during azacitidine treatment and for 3 months following the last dose, and must have a negative result of serum pregnancy test that was performed within 72 hours prior to starting study drug therapy. Exclusion Criteria: Any coexisting major illness or organ failure HIV positive, or active hepatitis B or C infection Uncontrolled acute infection Uncontrolled hemorrhage Pregnant or lactating Known or suspected hypersensitivity to azacitidine Patients diagnosed with malignant hepatic carcinoma or malignant disease within the past 12 months (except in situ carcinoma without complication, cervical or breast intraepithelial neoplasia, or other local malignant carcinoma that is likely to be treated by surgical removal or radiotherapy)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yoo-Jin Kim, MD, PhD

Phone

82-2-2258-6057

yoojink@catholic.ac.kr

First Name & Middle Initial & Last Name or Official Title & Degree

Kyungmin Kim

Phone

82-2-2258-7926

ddok9765@hotmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yoo-Jin Kim, MD, PhD

Organizational Affiliation

Division of hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Seoul St. Mary's Hospital

City

Seoul

ZIP/Postal Code

137-701

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yoo-Jin Kim, MD, PhD

Phone

82-2-2258-6057

yoojink@catholic.ac.kr

First Name & Middle Initial & Last Name & Degree

Kyungmin Kim

Phone

82-2-2258-7926

ddok9765@hotmail.com

Facility Name

Asan Medical Center

City

Seoul

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Je Hwan Lee, MD, PhD

Facility Name

Seoul National University Hospital

City

Seoul

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sung Soo Yoon, MD, PhD

12. IPD Sharing Statement

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5 Day Versus 7 Day Azacitidine in Lower Risk Myelodysplastic Syndrome

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