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

NCT ID: NCT01333449

Last Updated: 2014-06-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2013-08-31

Brief 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.

Detailed 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

Conditions

Myelodysplastic Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

Decitabine 20mg/m\^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

20mg/m\^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.

Interventions

Decitabine

20mg/m\^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.

Intervention Type: DRUG

Other Intervention Names

Dacogen

Eligibility Criteria

Inclusion Criteria

1. Newly diagnosed MDS patients aged 21 to 65 years belonging to any of the following categories: refractory cytopenia with multilineage dysplasia (RCMD) with or without ringed sideroblasts (i.e. RCMD and RCMD-RS), refractory anemia with excess blasts-1 (RAEB-1) or RAEB-2 if the prognostic scores are IPSS (international prognostic scoring system) Int-2 or IPSS-high or with WPSS (WHO prognostic scoring system) 3 and above

2. Therapy-related MDS with IPSS Int-2 and above or WPSS 3

3. Acceptable cardiac function MUGA or Echocardiography left ventricular ejection fraction of 40% and above

4. Acceptable lung function: FEV1>70% predicted, DLCO>60% predicted

5. Acceptable renal function: CCT > 50ml/min

6. Acceptable liver function: abnormalities in bilirubin or transaminases not > 2times upper limit of normal

7. Performance status of ECOG 2 or HCT-specific Comorbidity Index < 3

Exclusion Criteria

1. Any co-morbidity other than MDS which limits life-expectancy to <3mth

2. Diagnosis of other active cancer other than squamous cell carcinoma, basal cell carcinoma or carcinoma-in-situ 1 or 2 of the cervix

3. Presence of active infections not under control

4. Receipt of 5-azacytidine or other induction chemotherapy for MDS/AML

5. Patients not keen to explore allogeneic HCT as part of curative treatment plan

6. Pregnancy

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson

INDUSTRY

Sponsor Role: collaborator

Singapore General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aloysius Ho

Role: PRINCIPAL_INVESTIGATOR

Singapore General Hospital

Locations

Singapore General Hospital

Singapore, Singapore, Singapore

Countries

Singapore

Other Identifiers

Decitabine01

Identifier Type: -

Identifier Source: org_study_id