Study of Decitabine Induction Prior to Allogeneic Hematopoietic Cell Transplant in Newly Diagnosed MDS Patients

Myelodysplastic Syndrome Clinical Trial

Official title: Prospective Phase II Study of Decitabine Induction Therapy to Reduce Pre-transplant Disease Burden Prior to Allogeneic Hematopoietic Cell Transplant in Patients With Newly Diagnosed Myelodysplastic Syndromes.

Status Terminated

Clinical Trial Summary

Allogeneic blood stem cell transplant remains the only potential curative treatment for myelodysplastic syndromes (MDS) to date. Pre-transplant induction chemotherapy with leukemia-type regimens is associated with significant toxicity and even death. The hypomethylating agents decitabine and 5-azacytidine have been shown in studies to cause improved hematologic parameters and partial or complete responses in patients with high risk MDS compared to standard therapy. In contrast to leukemia-type chemotherapy, decitabine is associated with a relatively low risk of toxicity. We therefore propose to treat transplant-eligible MDS patients with Decitabine as induction therapy and a bridge to transplant.

Hypothesis:

1. Decitabine is able to reduce disease burden as measured by blood and marrow blast counts prior to allogeneic hematopoietic stem cell transplant to below 5%.

2. Decitabine is well-tolerated by patients with high-risk MDS and will be a safe induction agent and bridge prior to allogeneic transplant in transplant-eligible patients.

Clinical Trial Description

Primary endpoint:

1. safety and tolerability of Decitabine prior to transplant (assessed by occurence of non-hematologic toxicities of grade 3 or more as defined by CTC grading)

2. reduction in pre-transplant disease burden ability to achieve blast <5% in the bone marrow and peripheral blood

Secondary endpoints:

1. Proportion of patients with suitable donor able to proceed to an allogeneic hematopoietic cell transplant.

2. Non-relapse mortality

3. time to neutrophil engraftment

4. Overall survival and disease-free survival.

Patients will receive Decitabine until blast <5% is achieved, suitable HLA-matched donor or umbilical cord blood is available up to a maximum of 6 cycles. Patient who progress on therapy or are unable to find a donor by 6 cycles will be removed from protocol. The method, conditioning regimen and choice of donor will be determined based on patient's age and functional status, and transplant physician's discretion. The available regimens are standardized within the center ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

• NCT number: NCT01333449
• Study type: Interventional
• Source: Singapore General Hospital
• Status: Terminated
• Phase: Phase 2
• Start date: July 2010
• Completion date: August 2013