Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

Nordic MDS Group

Status and phase

Completed

Phase 2

Conditions

Myelodysplastic Syndrome

Chronic Myelomonocytic Leukemia

Treatments

Drug: Azacitidine

Drug: Erythropoetin

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT01048034

NMDSG08A

2009-011483-11 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

30 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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