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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nordic MDS Group
ClinicalTrials.gov Identifier:
NCT01048034
First received: January 12, 2010
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Drug: Azacitidine
Drug: Erythropoetin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Nordic MDS Group:

Primary Outcome Measures:
  • Hemoglobin level [ Time Frame: Week 28 ] [ Designated as safety issue: Yes ]
  • Number of patients reaching transfusion independency after treatment with Azacitidine [ Time Frame: Week 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect on leucocyte, platelet count [ Time Frame: Week 28 and End of Trial ] [ Designated as safety issue: Yes ]
  • Effect on bone marrow morphology and cytogenetics [ Time Frame: Week 28 and End of Trial ] [ Designated as safety issue: Yes ]
  • Number of patients reaching transfusion independency after treatment with Azacitidine and Epo [ Time Frame: End of Trial ] [ Designated as safety issue: No ]
  • Effect on genetic and epigenetic profile [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
  • Hemoglobin level [ Time Frame: End of Trial ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: January 2010
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azacitidine +/- erythropoetin Drug: 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
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01048034

Locations
Denmark
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
Norway
Department of Medcine, Haukeland University Hospital
Bergen, Norway
Department of Hematology, Rikshospitalet University Hospital
Oslo, Norway
Sweden
Department of Medicine, Mälarsjukhuset Hospital
Eskilstuna, Sweden
Department of medicine, Falun Hospital
Falun, Sweden
Department of Medicine, Sahlgrenska University Hospital / Östra
Göteborg, 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
Sponsors and Collaborators
Nordic MDS Group
Investigators
Study Director: Magnus Tobiasson, M.D. Nordic MDS Group
  More Information

No publications provided

Responsible Party: Nordic MDS Group
ClinicalTrials.gov Identifier: NCT01048034     History of Changes
Other Study ID Numbers: NMDSG08A, 2009-011483-11
Study First Received: January 12, 2010
Last Updated: October 28, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by Nordic MDS Group:
Myelodysplastic syndrome
Chronic myelomonocytic leukemia
Transfusion therapy
Transfusion dependency
Hypomethylating therapy
Azacitidine
DNA-methylation
Epigenetic modifications

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Epoetin Alfa
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Hematinics
Hematologic Agents

ClinicalTrials.gov processed this record on July 23, 2014