Multicenter Study to Assess the Efficacy of Decitabine in the Treatment of Chronic Myelomonocytic Leukemia

Study Overview
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Brief Summary
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The study aims to assess the activity of decitabine in the treatment of CMML.

Official Title
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A Phase II Multicenter Open-label Study to Assess the Efficacy of Decitabine in the Treatment of Chronic Myelomonocytic Leukemia

Conditions
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Chronic Myelomonocytic Leukemia

Intervention / Treatment
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* Drug: Decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 and older CMML diagnosis according to WHO criteria If WBC<=12000/mm3:IPSS High or INT-2 If WBC>12000/mm3: at least two of the following criteria: Blast cells>5% in the bone marrow Citogenetic abnormality other then t(5;12) (q33;p13) Anemia (Hb<10g/dl) Thrombocytopenia (Plt<100000/mm3) Splenomegaly(>5cm below costal margin) Extramedullary localization Patients untretaed or previously treated with Hydroxyurea or Imatinib or Etoposide given orally or non intensive chemotherapy or intensive chemotherapy given more thann 3 months befor inclusion Performance Status ECOG 0,1 or 2 Estimated life expectancy>=6 months Adequate hepatic function: Total bilirubin < 1.5 times upper limit of normal (except moderate unconjugate hyperbilirubinemia due to intra medullary hemolysis) AST and ALT < 3 times limit of normal Adequate renal function: Serum creatinine < 1.5 times limit of normal Creatinine clearance > 30ml/min Informed consent Negative pregnancy test or adequate contraception methods Exclusion Criteria: Myeloproliferative/myelodisplastic syndome othe than CMML Acute blastic transformation of CMML with bone marrow blast cells>20% Patients eligible for allogenic bone marrow transplantation with identified donor CMML with t(5;12) o PDGFBR rearrangement Intensive chemotherapy given less than 3 months before Previous treatment with hypomethylating agent Age< 18 years old Pregnancy or breastfeeding Performance Status ECOG>2 Estimate life expectancy<6 months HIV infection Chronic active hepatitis secondary to HCV or HBV (HBSAq positive) Serious concomitantsystemic disorders, including active bacterial fungal or viral infection, that in the opinion of the investigator, would compromise the safety of the patient and/or his/her ability to complete the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decitabine<br>Eligible patients will recieve Dacogen 20mg/m2 in 1 hour iv infusion for 5 days every 28 days (1 cycle)plus Best Supportive Care.A total of 6 courses is planned. | Drug: Decitabine<br>* Decitabine will be administered at a dose of 20 mg/m2 infused over a 1 hour period once daily for 5 consecutive days. The totale amount per course is 100 mg/m2. Cycles will be administered every 4 weeks (1 cycle of 28 days).It is recommented that patients be treated for a minimum of 4 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the activity of decitabine in the treatment of CMML | Activity will be evaluated as percentage of patients achieving complete or partial remission according to the International Working Group response criteria in myelodysplasia | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to assess the activity of decitabine in the treatment of CMML in terms of overall survival, time to leukemic transormation, response duration in terms of time to relapse after CR, PR, time to disease progression, ecc |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Decitabine