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

NCT01048034 | Completed Phase 2 DMC

• 2 other identifiers: NMDSG08A2009-011483-11
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 17

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

Outcome Measures

Primary Outcomes (2)

• Hemoglobin level

  Week 28

• Number of patients reaching transfusion independency after treatment with Azacitidine

  Week 28

Secondary Outcomes (5)

• Effect on leucocyte, platelet count

  Week 28 and 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

• Hemoglobin level

  End of Trial

Study Arms (1)

Azacitidine +/- erythropoetin

EXPERIMENTAL

Drug: Azacitidine; Drug: Erythropoetin

Interventions

Azacitidine 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

Azacitidine +/- erythropoetin

Erythropoetin 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.

Azacitidine +/- erythropoetin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Serum creatinine \>2.0 mg/dL (177 micromol/L)
• 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)
• Serum total bilirubin \>1.5 mg/dL (26 micromol/L)
• Uncontrolled systemic infection
• Considered not capable of following the study protocol

Sponsors & Collaborators

• Nordic MDS Group: lead

Study Sites (17)

Department of Hematology, Aalborg University Hospital

Aalborg, Denmark

Location

Department of Hematology, Aarhus Univsersity Hospital

Aarhus, Denmark

Location

Department of Hematology, Rigshospitalet Univsersity Hospital

Copenhagen, Denmark

Location

Department of Hematology, Herlev Hospital

Herlev, Denmark

Location

Department of Hematology, Odense University Hospital

Odense, Denmark

Location

Department of Medcine, Haukeland University Hospital

Bergen, Norway

Location

Department of Hematology, Rikshospitalet University Hospital

Oslo, Norway

Location

Department of Medicine, Mälarsjukhuset Hospital

Eskilstuna, Sweden

Location

Department of medicine, Falun Hospital

Falun, Sweden

Location

Department of Medicine, Sahlgrenska University Hospital / Östra

Gothenburg, Sweden

Location

Department of Hematology, Linköping University Hospital

Linköping, Sweden

Location

Department of Medicine, Sunderbyn Hospital

Luleå, Sweden

Location

Department of Hematology, Lund University Hospital

Lund, Sweden

Location

Department of Hematology, Karolinska University Hospital

Stockholm, Sweden

Location

Department of Medicine, Södersjukhuset Hospital

Stockholm, Sweden

Location

Department of Medicine, Umeå University Hospital

Umeå, Sweden

Location

Department of Medicine, Uppsala University Hospital

Uppsala, Sweden

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

Azacitidine; Erythropoietin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Magnus Tobiasson, M.D.

  Nordic MDS Group

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 13, 2010
• Study Start: January 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 29, 2013

Record last verified: 2013-10

Locations

DK (5); SE (10); NO (2)