Back to resultsEvaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
Primary Purpose
Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Azacitidine
Erythropoetin
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring Myelodysplastic syndrome, Chronic myelomonocytic leukemia, Transfusion therapy, Transfusion dependency, Hypomethylating therapy, Azacitidine, DNA-methylation, Epigenetic modifications
Eligibility Criteria
Inclusion Criteria:
- Must be 18 years of age at the time of signing the informed consent form
- MDS at IPSS Low or Int-1, or mixed MDS/MPD; either CMML with < 10% marrow blasts or RARS-T
- Patients with high or intermediate probability for response according to the predictive model (see Hellstrom-Lindberg et al, Br J Haematol 99:344-51 1997)should be refractory to EPO / darbepoetin (equivalent to > 60 000 U of EPO / week for > 8 weeks) followed by EPO + G-CSF for > 8 weeks, or biosimilar drugs in equipotent doses, or EPO + G-CSF upfront for 8 weeks. Patients with low probability for response according to the predictive model, could be included without prior EPO/G-CSF treatment
- Transfusion need >4 units over the last 8 weeks, or >8 units over the last 26 weeks.
- Subject has signed the informed consent document.
- Men and women of childbearing potential must use effective contraception during, and for up to 3 months after treatment.
Exclusion Criteria:
- Pregnant or lactating females.
- Patients who are eligible for curative treatment
- Expected survival less than 24 weeks.
- Symptomatic thrombocytopenia / active bleeding
- Patients with JAK-2 positive RARS-T if eligible for new investigational drugs
Serum biochemical values as follows
- Serum creatinine >2.0 mg/dL (177 micromol/L)
- Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN)
- Serum total bilirubin >1.5 mg/dL (26 micromol/L)
- Uncontrolled systemic infection
- Considered not capable of following the study protocol
Sites / Locations
- Department of Hematology, Aalborg University Hospital
- Department of Hematology, Aarhus Univsersity Hospital
- Department of Hematology, Rigshospitalet Univsersity Hospital
- Department of Hematology, Herlev Hospital
- Department of Hematology, Odense University Hospital
- Department of Medcine, Haukeland University Hospital
- Department of Hematology, Rikshospitalet University Hospital
- Department of Medicine, Mälarsjukhuset Hospital
- Department of medicine, Falun Hospital
- Department of Medicine, Sahlgrenska University Hospital / Östra
- Department of Hematology, Linköping University Hospital
- Department of Medicine, Sunderbyn Hospital
- Department of Hematology, Lund University Hospital
- Department of Hematology, Karolinska University Hospital
- Department of Medicine, Södersjukhuset Hospital
- Department of Medicine, Umeå University Hospital
- Department of Medicine, Uppsala University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Azacitidine +/- erythropoetin
Arm Description
Outcomes
Primary Outcome Measures
Hemoglobin level
Number of patients reaching transfusion independency after treatment with Azacitidine
Secondary Outcome Measures
Effect on leucocyte, platelet count
Effect on bone marrow morphology and cytogenetics
Number of patients reaching transfusion independency after treatment with Azacitidine and Epo
Effect on genetic and epigenetic profile
Hemoglobin level
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01048034
Brief Title
Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
Official Title
Clinical and Biological Evaluation of Azacitidine in Transfusion-dependent Patients With Low and Intermediate-1 Risk MDS, and Low-risk CMML, Who Are Either Refractory to or Not Eligible for Treatment With Erythropoietin +/- G-CSF
Study Type
Interventional
2. Study Status
Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nordic MDS Group
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Azacitidine has proved prolonged overall survival in patients with high-risk MDS. Minor pilot studies have shown that treatment with Azacitidine can induce transfusion independency in previous transfusion dependent patients with low-risk MDS. This study will evaluate the effect of Azacitidine in transfusion dependent patients with low-risk MDS (IPSS low or int-1) or low risk CMML. Included patients should first have failed, or considered not being eligible to, treatment with EPO +/- G-CSF. Our hypothesis is that Azacitidine can lead to transfusion independency in this group of patients. Those patients who do not respond to treatment with Azacitidine alone, will be given treatment with the combination of Azacitidine and EPO where our hypothesis is that Azacitidine can restore sensitivity to EPO.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia
Keywords
Myelodysplastic syndrome, Chronic myelomonocytic leukemia, Transfusion therapy, Transfusion dependency, Hypomethylating therapy, Azacitidine, DNA-methylation, Epigenetic modifications
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Azacitidine +/- erythropoetin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Intervention Description
100 mg / m(2) subcutaneously day 1-5 every 4 weeks for 6 cycles. Another three cycles will be given together with epo for those not responding to the first 6 cycles of Azacitidine
Intervention Type
Drug
Intervention Name(s)
Erythropoetin
Intervention Description
For those patients not responding to Azacitidine alone, the combination of Azacitidine and erythropoetin 60 000 U / week for 16 weeks will be given.
Primary Outcome Measure Information:
Title
Hemoglobin level
Time Frame
Week 28
Title
Number of patients reaching transfusion independency after treatment with Azacitidine
Time Frame
Week 28
Secondary Outcome Measure Information:
Title
Effect on leucocyte, platelet count
Time Frame
Week 28 and End of Trial
Title
Effect on bone marrow morphology and cytogenetics
Time Frame
Week 28 and End of Trial
Title
Number of patients reaching transfusion independency after treatment with Azacitidine and Epo
Time Frame
End of Trial
Title
Effect on genetic and epigenetic profile
Time Frame
Week 28
Title
Hemoglobin level
Time Frame
End of Trial
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must be 18 years of age at the time of signing the informed consent form
MDS at IPSS Low or Int-1, or mixed MDS/MPD; either CMML with < 10% marrow blasts or RARS-T
Patients with high or intermediate probability for response according to the predictive model (see Hellstrom-Lindberg et al, Br J Haematol 99:344-51 1997)should be refractory to EPO / darbepoetin (equivalent to > 60 000 U of EPO / week for > 8 weeks) followed by EPO + G-CSF for > 8 weeks, or biosimilar drugs in equipotent doses, or EPO + G-CSF upfront for 8 weeks. Patients with low probability for response according to the predictive model, could be included without prior EPO/G-CSF treatment
Transfusion need >4 units over the last 8 weeks, or >8 units over the last 26 weeks.
Subject has signed the informed consent document.
Men and women of childbearing potential must use effective contraception during, and for up to 3 months after treatment.
Exclusion Criteria:
Pregnant or lactating females.
Patients who are eligible for curative treatment
Expected survival less than 24 weeks.
Symptomatic thrombocytopenia / active bleeding
Patients with JAK-2 positive RARS-T if eligible for new investigational drugs
Serum biochemical values as follows
Serum creatinine >2.0 mg/dL (177 micromol/L)
Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN)
Serum total bilirubin >1.5 mg/dL (26 micromol/L)
Uncontrolled systemic infection
Considered not capable of following the study protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Magnus Tobiasson, M.D.
Organizational Affiliation
Nordic MDS Group
Official's Role
Study Director
Facility Information:
Facility Name
Department of Hematology, Aalborg University Hospital
City
Aalborg
Country
Denmark
Facility Name
Department of Hematology, Aarhus Univsersity Hospital
City
Aarhus
Country
Denmark
Facility Name
Department of Hematology, Rigshospitalet Univsersity Hospital
City
Copenhagen
Country
Denmark
Facility Name
Department of Hematology, Herlev Hospital
City
Herlev
Country
Denmark
Facility Name
Department of Hematology, Odense University Hospital
City
Odense
Country
Denmark
Facility Name
Department of Medcine, Haukeland University Hospital
City
Bergen
Country
Norway
Facility Name
Department of Hematology, Rikshospitalet University Hospital
City
Oslo
Country
Norway
Facility Name
Department of Medicine, Mälarsjukhuset Hospital
City
Eskilstuna
Country
Sweden
Facility Name
Department of medicine, Falun Hospital
City
Falun
Country
Sweden
Facility Name
Department of Medicine, Sahlgrenska University Hospital / Östra
City
Göteborg
Country
Sweden
Facility Name
Department of Hematology, Linköping University Hospital
City
Linköping
Country
Sweden
Facility Name
Department of Medicine, Sunderbyn Hospital
City
Luleå
Country
Sweden
Facility Name
Department of Hematology, Lund University Hospital
City
Lund
Country
Sweden
Facility Name
Department of Hematology, Karolinska University Hospital
City
Stockholm
Country
Sweden
Facility Name
Department of Medicine, Södersjukhuset Hospital
City
Stockholm
Country
Sweden
Facility Name
Department of Medicine, Umeå University Hospital
City
Umeå
Country
Sweden
Facility Name
Department of Medicine, Uppsala University Hospital
City
Uppsala
Country
Sweden
12. IPD Sharing Statement
Learn more about this trial
Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
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