Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-31

Study Completion Date

2012-08-31

Brief Summary

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RATIONALE: Decitabine may help myelodysplastic cells become more like normal stem cells. PURPOSE: This clinical trial studies differentiation therapy with decitabine in treating patients with myelodysplastic syndrome.

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Detailed Description

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PRIMARY OBJECTIVES:

I. Demonstrate that differentiation therapy with DNMT1 depleting but non-DNA damaging doses of decitabine is efficacious and can be administered weekly for \> = 12 months. SECONDARY OBJECTIVES: I. Assess safety of the regimen.

II. Retrospectively compare study and standard regimen clinical responses. III. Assess the ability of a pharmacodynamic assay that measures DNMT1 depletion in peripheral blood white blood cells to predict clinical responses to decitabine.

IV. Assess PCR for aberrant methylation signature as an early marker of relapse. V. Identify biologic features of MDS that correlate with response to decitabine, thereby facilitating future patient selection.

VI. In cases of relapse or resistance, assess the role of the enzyme CDA in altering decitabine metabolism and preventing DNMT1 depletion.

OUTLINE:

INDUCTION PHASE: Patients receive decitabine subcutaneously (SC) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%.

MAINTENANCE PHASE: Patients then receive decitabine SC twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Conditions

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Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndromes Myelodysplastic Syndromes Refractory Anemia Refractory Anemia With Excess Blasts Refractory Anemia With Ringed Sideroblasts Refractory Cytopenia With Multilineage Dysplasia Thrombocytopenia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I: decitabine

INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

flow cytometry

Intervention Type OTHER

Correlative studies

DNA methylation analysis

Intervention Type OTHER

Correlative studies

cytogenetic analysis

Intervention Type OTHER

Correlative studies

decitabine

Intervention Type DRUG

Given subcutaneously

microarray analysis

Intervention Type GENETIC

Correlative studies

gene expression analysis

Intervention Type GENETIC

Correlative studies

pharmacological study

Intervention Type OTHER

Correlative studies

polymorphism analysis

Intervention Type GENETIC

Correlative studies

Interventions

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flow cytometry

Correlative studies

Intervention Type OTHER

DNA methylation analysis

Correlative studies

Intervention Type OTHER

cytogenetic analysis

Correlative studies

Intervention Type OTHER

decitabine

Given subcutaneously

Intervention Type DRUG

microarray analysis

Correlative studies

Intervention Type GENETIC

gene expression analysis

Correlative studies

Intervention Type GENETIC

pharmacological study

Correlative studies

Intervention Type OTHER

polymorphism analysis

Correlative studies

Intervention Type GENETIC

Other Intervention Names

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5-aza-dCyd 5AZA DAC Dacogen deoxyazacytidine dezocitidine gene expression profiling pharmacological studies

Eligibility Criteria

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Inclusion Criteria

* MDS classified by hematopathology review as WHO categories refractory anemia (RA) or refractory cytopenia with multi-lineage dysplasia (RCMD) or refractory anemia with ring sideroblasts (RARS) or refractory anemia with excess blasts (RAEB1 or RAEB2) or chronic myelo-monocytic leukemia (CMML1 or CMML2)
* Symptomatic anemia OR thrombocytopenia with a platelet count of \< 100 x 10\^9/L OR transfusion dependence for red-cells OR transfusion dependence for platelets OR absolute neutrophil count \< 1 x 10\^9/L

Exclusion

* MDS of the WHO sub-types RA or RCMD with sole 5q- abnormality on cytogenetics unless failed lenalidomide (Revlimid) therapy
* Previous treatment with decitabine
* Untreated erythropoietin deficiency defined as an erythropoietin level of \< 200 IU/L and erythropoietin replacement therapy for \< 8 weeks (erythropoietin deficiency until corrected)
* Uncontrolled infection
* Severe sepsis or septic shock
* Current pregnancy or breast feeding
* The patient is of childbearing age, and is unwilling to use contraception and has not had a tubal ligation, hysterectomy, or vasectomy , or their partner is also unwilling to use an acceptable method of contraception as determined by the investigator
* Not able to give informed consent
* Altered mental status or seizure disorder
* ALT \> 300 IU; or albumin \< 2.0 mg/dL
* Creatinine \> 2.5 mg/dl and creatinine clearance \< 60ml/min
* B12, folate, or iron deficient, until corrected
* NYHA class III/IV status
* ECOG performance status \> 2
* HIV positive or history of seropositivity for HIV
* Transformation to acute leukemia ( \>= 20% myelo-blasts in marrow aspirate)
* Any experimental agents other than the study drug decitabine

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No