NMDSG08A. 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.
Sponsor : Nordic MDS group
Principal investigator : Eva Hellström-Lindberg
Status : 30 patients enrolled. Closed for inclusion August, 2011.
Start : January 2010
Inclusion criteria :
- Must be ³18 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 model2 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
Primary endpoint : number of patients reaching transfusion independency
Treatment : Azacitidine 75mg/m(2) for 6 cycles. Another 2 cycles with the addition of EPO for those not responding to the first 6 cycles.
Report: Abstract EHA Tobiasson, M et al; "Evaluation of Azacitidine in transfusion-dependent, Epo-refractory patients with lower-risk MDS."