Clinical trial NCT01048034: Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Keywords: Myelodysplastic syndrome
Chronic myelomonocytic leukemia
Transfusion therapy
Transfusion dependency
Hypomethylating therapy
Azacitidine
DNA-methylation
Epigenetic modifications
Lead sponsor: Nordic MDS Group
Sponsor class: NETWORK
First posted: 2010-01-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Hemoglobin level
timeFrame: Week 28
measure: Number of patients reaching transfusion independency after treatment with Azacitidine
timeFrame: Week 28
Secondary outcomes:
measure: Effect on leucocyte, platelet count
timeFrame: Week 28 and End of Trial
measure: Effect on bone marrow morphology and cytogenetics
timeFrame: Week 28 and End of Trial
measure: Number of patients reaching transfusion independency after treatment with Azacitidine and Epo
timeFrame: End of Trial
measure: Effect on genetic and epigenetic profile
timeFrame: Week 28
measure: Hemoglobin level
timeFrame: End of Trial
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Hematology, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Department of Hematology, Aarhus Univsersity Hospital
city: Copenhagen
country: Denmark
facility: Department of Hematology, Rigshospitalet Univsersity Hospital
city: Herlev
country: Denmark
facility: Department of Hematology, Herlev Hospital
city: Odense
country: Denmark
facility: Department of Hematology, Odense University Hospital
city: Bergen
country: Norway
facility: Department of Medcine, Haukeland University Hospital
city: Oslo
country: Norway
facility: Department of Hematology, Rikshospitalet University Hospital
city: Eskilstuna
country: Sweden
facility: Department of Medicine, Mälarsjukhuset Hospital
city: Falun
country: Sweden
facility: Department of medicine, Falun Hospital
city: Göteborg
country: Sweden
facility: Department of Medicine, Sahlgrenska University Hospital / Östra
city: Linköping
country: Sweden
facility: Department of Hematology, Linköping University Hospital
city: Luleå
country: Sweden
facility: Department of Medicine, Sunderbyn Hospital
city: Lund
country: Sweden
facility: Department of Hematology, Lund University Hospital
city: Stockholm
country: Sweden
facility: Department of Hematology, Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Department of Medicine, Södersjukhuset Hospital
city: Umeå
country: Sweden
facility: Department of Medicine, Umeå University Hospital
city: Uppsala
country: Sweden
facility: Department of Medicine, Uppsala University Hospital
Study officials:
affiliation: Nordic MDS Group
name: Magnus Tobiasson, M.D.
role: STUDY_DIRECTOR
References: