Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
Information source: Nordic MDS Group
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia
Intervention: Azacitidine (Drug); Erythropoetin (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Nordic MDS Group Official(s) and/or principal investigator(s): Magnus Tobiasson, M.D., Study Director, Affiliation: Nordic MDS Group
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.
Clinical Details
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 design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Hemoglobin levelNumber of patients reaching transfusion independency after treatment with Azacitidine
Secondary outcome: Effect on leucocyte, platelet countEffect 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
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
1. Serum creatinine >2. 0 mg/dL (177 micromol/L)
2. 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)
3. Serum total bilirubin >1. 5 mg/dL (26 micromol/L)
- Uncontrolled systemic infection
- Considered not capable of following the study protocol
Locations and Contacts
Department of Hematology, Aalborg University Hospital, Aalborg, Denmark
Department of Hematology, Aarhus Univsersity Hospital, Aarhus, Denmark
Department of Hematology, Rigshospitalet Univsersity Hospital, Copenhagen, Denmark
Department of Hematology, Herlev Hospital, Herlev, Denmark
Department of Hematology, Odense University Hospital, Odense, Denmark
Department of Medcine, Haukeland University Hospital, Bergen, Norway
Department of Hematology, Rikshospitalet University Hospital, Oslo, Norway
Department of Medicine, Mälarsjukhuset Hospital, Eskilstuna, Sweden
Department of medicine, Falun Hospital, Falun, Sweden
Department of Medicine, Sahlgrenska University Hospital / Östra, Göteborg, Sweden
Department of Hematology, Linköping University Hospital, Linköping, Sweden
Department of Medicine, Sunderbyn Hospital, Luleå, Sweden
Department of Hematology, Lund University Hospital, Lund, Sweden
Department of Hematology, Karolinska University Hospital, Stockholm, Sweden
Department of Medicine, Södersjukhuset Hospital, Stockholm, Sweden
Department of Medicine, Umeå University Hospital, Umeå, Sweden
Department of Medicine, Uppsala University Hospital, Uppsala, Sweden
Additional Information
Starting date: January 2010
Last updated: October 28, 2013
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