Deferasirox in Treating Patients With Very Low, Low, or Intermediate-Risk Red Blood Cell Transfusion Dependent Anemia or Myelodysplastic Syndrome
Primary Purpose
Anemia, Myelodysplastic Syndrome
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Deferasirox
Laboratory Biomarker Analysis
Sponsored by
About this trial
This is an interventional treatment trial for Anemia
Eligibility Criteria
Inclusion Criteria:
- Capable of giving written informed consent prior to any study-specific procedures
- Diagnosis of MDS as defined by the World Health Organization (WHO) diagnostic criteria
- Have very low, low or intermediate-risk disease by the Revised International Prognostic Scoring System (IPSS-R)
- Baseline serum ferritin level >= 100 ng/mL
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Anemia defined as: hemoglobin =< 10.0 g/dL
- Bilirubin =< 1.5 times upper limit of normal (ULN)
- Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =< 3.5 times ULN
- Serum creatinine =< 1.5 x ULN
- Estimated glomerular filtration rate (GFR) > 40 mL/min
Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of deferasirox
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment; effective contraception methods include:
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
- Total abstinence or (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject
- Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential; sexually active males must use a condom during intercourse while taking drug and for 28 days after stopping study medication and should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
- Females with childbearing potential* must have had a negative urine or serum pregnancy test =< 7 days before the first dose of deferasirox and must also not be breastfeeding
- Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Exclusion Criteria:
- If the patient is currently receiving erythroid stimulating agents (ESA) with plans to continue during study, less than 2 months duration of ESA prior to starting study drug and no dose escalation within 2 months of start of study drug
- If the patient is being treated with granulocyte-colony stimulating factor (GCSF) and/or a TPO-mimetic (for example, eltrombopag or romiplostim) with plans to continue during the study: Less than 2 months duration of GCSF or the TPO-mimetic treatment prior to starting study drug; or GCSF and/or TPO-mimetic has been added to ESA therapy within 2 months of start of study drug
- If patient is being treated with lenalidomide with plans to continue during the study: Stable dose for less than 3 months prior to start of study drug
- If patient is being treated with hypomethylating agents (HMA) (for example, azacitidine or decitabine) with plans to continue during the study: Stable dose for less than 6 months prior to start of study drug
- Currently enrolled in, or discontinued within the last 14 days from a clinical trial involving an investigational product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- Presence of >= 10% blast by morphologic examination of bone marrow aspirate or biopsy
- Platelets =< 50,000
- Microcytosis on screening blood cell count (CBC) (mean corpuscular volume [MCV] < 81 fL)
- Active gastrointestinal (GI) ulceration or hemorrhage
- Have a serious preexisting medical condition that, in the opinion of the investigator would preclude participation in the study (for example a GI disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome) or that would result in a life expectancy of less than 1 year
- Known hypersensitivity to deferasirox
- History of non-transfusional hemosiderosis
- Prior hematopoietic stem cell transplant for the diagnosis of MDS
- A second primary malignancy that in the judgment of the principal investigator (PI) or designee may affect the interpretation of results
- Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis
- Currently using aluminum-containing antacid products
- History of clinically significant auditory or ocular toxicity with ICT
Sites / Locations
- Fred Hutch/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (deferasirox)
Arm Description
Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Proportion of Patients That Achieve Erythroid Hematologic Improvement.
As defined by the modified International Working Group (IWG) response criteria:
Erythroid response (pretreatment, <11 g/dL):
Hgb increase by ≥ 1.5 g/dL
Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation.
Platelet response (pretreatment, < 100 x 10^9/L)
Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets
Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100%
Neutrophil response (pretreatment, < 1.0 x 10^9/L)
1) At least 100% increase and an absolute increase > 0.5 x 10^9/L
Secondary Outcome Measures
Change in Red Blood Cell (RBC) Transfusion Requirements
Assessed monthly for up to twelve months.
Change in Serum Ferritin Levels
Assessed monthly for up to twelve months.
Proportion of Patients Who Achieve Granulocyte or Platelet Hematologic Improvement
As defined by the modified International Working Group (IWG) response criteria:
Erythroid response (pretreatment, <11 g/dL):
Hgb increase by ≥ 1.5 g/dL
Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation.
Platelet response (pretreatment, < 100 x 10^9/L)
Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets
Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100%
Neutrophil response (pretreatment, < 1.0 x 10^9/L)
1) At least 100% increase and an absolute increase > 0.5 x 10^9/L
Full Information
NCT ID
NCT02943668
First Posted
October 21, 2016
Last Updated
June 12, 2020
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI), Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02943668
Brief Title
Deferasirox in Treating Patients With Very Low, Low, or Intermediate-Risk Red Blood Cell Transfusion Dependent Anemia or Myelodysplastic Syndrome
Official Title
A Phase II Study of Deferasirox in Patients With Myelodysplastic Syndromes Who Are Anemic With Iron Overload
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to low accrual
Study Start Date
March 2, 2017 (Actual)
Primary Completion Date
December 17, 2018 (Actual)
Study Completion Date
December 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI), Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase II trial studies how well deferasirox works in treating patients with very low, low, or intermediate-risk anemia or myelodysplastic syndrome that depends on red blood cell transfusions. Deferasirox may treat too much iron in the blood caused by blood transfusions.
Detailed Description
PRIMARY OBJECTIVES:
I. To assess the activity of iron chelation therapy (ICT) with deferasirox, in patients with anemia due to myelodysplastic syndrome (MDS).
SECONDARY OBJECTIVES:
I. Reduction in red blood cell (RBC) transfusion requirements. II. Hematologic improvement. III. Change in serum ferritin levels from baseline to the end of the study as measured on a monthly basis.
IV. Safety and tolerability of deferasirox.
EXPLORATORY OBJECTIVES:
I. Blood and marrow samples will be taken to study erythropoiesis and the impact of iron overload on erythropoiesis.
OUTLINE: Patients receive deferasirox orally (PO) once daily (QD). Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (deferasirox)
Arm Type
Experimental
Arm Description
Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Deferasirox
Other Intervention Name(s)
Exjade
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Proportion of Patients That Achieve Erythroid Hematologic Improvement.
Description
As defined by the modified International Working Group (IWG) response criteria:
Erythroid response (pretreatment, <11 g/dL):
Hgb increase by ≥ 1.5 g/dL
Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation.
Platelet response (pretreatment, < 100 x 10^9/L)
Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets
Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100%
Neutrophil response (pretreatment, < 1.0 x 10^9/L)
1) At least 100% increase and an absolute increase > 0.5 x 10^9/L
Time Frame
At 6 months
Secondary Outcome Measure Information:
Title
Change in Red Blood Cell (RBC) Transfusion Requirements
Description
Assessed monthly for up to twelve months.
Time Frame
Baseline up to 12 months
Title
Change in Serum Ferritin Levels
Description
Assessed monthly for up to twelve months.
Time Frame
Baseline up to 12 months
Title
Proportion of Patients Who Achieve Granulocyte or Platelet Hematologic Improvement
Description
As defined by the modified International Working Group (IWG) response criteria:
Erythroid response (pretreatment, <11 g/dL):
Hgb increase by ≥ 1.5 g/dL
Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation.
Platelet response (pretreatment, < 100 x 10^9/L)
Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets
Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100%
Neutrophil response (pretreatment, < 1.0 x 10^9/L)
1) At least 100% increase and an absolute increase > 0.5 x 10^9/L
Time Frame
At 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Capable of giving written informed consent prior to any study-specific procedures
Diagnosis of MDS as defined by the World Health Organization (WHO) diagnostic criteria
Have very low, low or intermediate-risk disease by the Revised International Prognostic Scoring System (IPSS-R)
Baseline serum ferritin level >= 100 ng/mL
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Anemia defined as: hemoglobin =< 10.0 g/dL
Bilirubin =< 1.5 times upper limit of normal (ULN)
Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =< 3.5 times ULN
Serum creatinine =< 1.5 x ULN
Estimated glomerular filtration rate (GFR) > 40 mL/min
Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of deferasirox
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment; effective contraception methods include:
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Total abstinence or (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential; sexually active males must use a condom during intercourse while taking drug and for 28 days after stopping study medication and should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
Females with childbearing potential* must have had a negative urine or serum pregnancy test =< 7 days before the first dose of deferasirox and must also not be breastfeeding
Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Exclusion Criteria:
If the patient is currently receiving erythroid stimulating agents (ESA) with plans to continue during study, less than 2 months duration of ESA prior to starting study drug and no dose escalation within 2 months of start of study drug
If the patient is being treated with granulocyte-colony stimulating factor (GCSF) and/or a TPO-mimetic (for example, eltrombopag or romiplostim) with plans to continue during the study: Less than 2 months duration of GCSF or the TPO-mimetic treatment prior to starting study drug; or GCSF and/or TPO-mimetic has been added to ESA therapy within 2 months of start of study drug
If patient is being treated with lenalidomide with plans to continue during the study: Stable dose for less than 3 months prior to start of study drug
If patient is being treated with hypomethylating agents (HMA) (for example, azacitidine or decitabine) with plans to continue during the study: Stable dose for less than 6 months prior to start of study drug
Currently enrolled in, or discontinued within the last 14 days from a clinical trial involving an investigational product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Presence of >= 10% blast by morphologic examination of bone marrow aspirate or biopsy
Platelets =< 50,000
Microcytosis on screening blood cell count (CBC) (mean corpuscular volume [MCV] < 81 fL)
Active gastrointestinal (GI) ulceration or hemorrhage
Have a serious preexisting medical condition that, in the opinion of the investigator would preclude participation in the study (for example a GI disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome) or that would result in a life expectancy of less than 1 year
Known hypersensitivity to deferasirox
History of non-transfusional hemosiderosis
Prior hematopoietic stem cell transplant for the diagnosis of MDS
A second primary malignancy that in the judgment of the principal investigator (PI) or designee may affect the interpretation of results
Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis
Currently using aluminum-containing antacid products
History of clinically significant auditory or ocular toxicity with ICT
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bart Scott
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Deferasirox in Treating Patients With Very Low, Low, or Intermediate-Risk Red Blood Cell Transfusion Dependent Anemia or Myelodysplastic Syndrome
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