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

Phase 2

Completed

• Conditions: Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia
• Interventions: Drug: Azacitidine; Drug: Erythropoetin

• Registration Number: NCT01048034
• Lead Sponsor: Nordic MDS Group

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01
• Study First Submitted: 2010-01-12
• Study First Submitted QC: 2010-01-12
• Study First Posted: 2010-01-13
• Primary Completion: 2012-08
• Study Completion: 2012-08
• Status Verified: 2013-10
• Last Update Submitted: 2013-10-28
• Last Update Posted: 2013-10-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Azacitidine +/- erythropoetin	Erythropoetin	-
Azacitidine +/- erythropoetin	Azacitidine	-

Primary Outcome Measures

Name	Time	Method
Number of patients reaching transfusion independency after treatment with Azacitidine	Week 28
Hemoglobin level	Week 28

Secondary Outcome Measures

Name	Time	Method
Effect on leucocyte, platelet count	Week 28 and End of Trial
Hemoglobin level	End of Trial
Effect on bone marrow morphology and cytogenetics	Week 28 and End of Trial
Number of patients reaching transfusion independency after treatment with Azacitidine and Epo	End of Trial
Effect on genetic and epigenetic profile	Week 28

Trial Locations

Locations (17)

Department of Hematology, Aarhus Univsersity Hospital; 🇩🇰 Aarhus, Denmark

Department of Hematology, Linköping University Hospital; 🇸🇪 Linköping, Sweden

Department of medicine, Falun Hospital; 🇸🇪 Falun, Sweden

Department of Medicine, Sunderbyn Hospital; 🇸🇪 Luleå, Sweden

Department of Medicine, Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Department of Hematology, Rigshospitalet Univsersity Hospital; 🇩🇰 Copenhagen, Denmark

Department of Hematology, Lund University Hospital; 🇸🇪 Lund, Sweden

Department of Hematology, Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

Department of Hematology, Aalborg University Hospital; 🇩🇰 Aalborg, 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 Medicine, Mälarsjukhuset Hospital; 🇸🇪 Eskilstuna, Sweden

Department of Medicine, Sahlgrenska University Hospital / Östra; 🇸🇪 Göteborg, Sweden

Department of Medicine, Södersjukhuset Hospital; 🇸🇪 Stockholm, Sweden

Department of Medicine, Umeå University Hospital; 🇸🇪 Umeå, Sweden

Department of Hematology, Rikshospitalet University Hospital; 🇳🇴 Oslo, Norway