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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01048034
First Posted: January 13, 2010
Last Update Posted: October 29, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Nordic MDS Group
  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: Intervention Model: Single Group Assignment
Masking: None (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 ]
  • Number of patients reaching transfusion independency after treatment with Azacitidine [ Time Frame: Week 28 ]

Secondary Outcome Measures:
  • Effect on leucocyte, platelet count [ Time Frame: Week 28 and End of Trial ]
  • Effect on bone marrow morphology and cytogenetics [ Time Frame: Week 28 and End of Trial ]
  • Number of patients reaching transfusion independency after treatment with Azacitidine and Epo [ Time Frame: End of Trial ]
  • Effect on genetic and epigenetic profile [ Time Frame: Week 28 ]
  • Hemoglobin level [ Time Frame: End of Trial ]

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

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: Nordic MDS Group
ClinicalTrials.gov Identifier: NCT01048034     History of Changes
Other Study ID Numbers: NMDSG08A
2009-011483-11 ( EudraCT Number )
First Submitted: January 12, 2010
First Posted: January 13, 2010
Last Update Posted: October 29, 2013
Last Verified: October 2013

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:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Azacitidine
Epoetin Alfa
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Hematinics