NCT01165996

Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome

A Proof of Concept Study of Non-DNA Damaging DNMT1 Depletion Therapy for Myelodysplastic Syndrome

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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

• 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

Interventions

Type	Name	Description
OTHER	flow cytometry	Correlative studies
OTHER	DNA methylation analysis	Correlative studies
OTHER	cytogenetic analysis	Correlative studies
DRUG	decitabine	Given subcutaneously
GENETIC	microarray analysis	Correlative studies
GENETIC	gene expression analysis	Correlative studies
OTHER	pharmacological study	Correlative studies
GENETIC	polymorphism analysis	Correlative studies

Timeline

• Start date: 2010-07-01
• Primary completion: 2011-12-01
• Completion: 2012-08-01
• First posted: 2010-07-20
• Last updated: 2019-03-04
• Results posted: 2013-02-26

Locations

2 sites across 1 country: United States