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

NCT ID: NCT01048034

Last Updated: 2013-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2012-08-31

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.

Conditions

Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia

Keywords

Myelodysplastic syndrome; Chronic myelomonocytic leukemia; Transfusion therapy; Transfusion dependency; Hypomethylating therapy; Azacitidine; DNA-methylation; Epigenetic modifications

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azacitidine +/- erythropoetin

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

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

Erythropoetin

Intervention Type: DRUG

For those patients not responding to Azacitidine alone, the combination of Azacitidine and erythropoetin 60 000 U / week for 16 weeks will be given.

Interventions

Azacitidine

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

Erythropoetin

For those patients not responding to Azacitidine alone, the combination of Azacitidine and erythropoetin 60 000 U / week for 16 weeks will be given.

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nordic MDS Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Magnus Tobiasson, M.D.

Role: STUDY_DIRECTOR

Nordic MDS Group

Locations

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

Gothenburg, , 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

Countries

Denmark; Norway; Sweden

Other Identifiers

2009-011483-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NMDSG08A

Identifier Type: -

Identifier Source: org_study_id