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

Sponsor

Singapore General Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT01333449

Collaborator

Johnson & Johnson (Industry)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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:

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%.
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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome	Drug: Decitabine	Phase 2

Detailed Description

Primary endpoint:

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

Secondary endpoints:

Proportion of patients with suitable donor able to proceed to an allogeneic hematopoietic cell transplant.
Non-relapse mortality
time to neutrophil engraftment
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

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Study Start Date :

Jul 1, 2010

Actual Primary Completion Date :

Aug 1, 2013

Actual Study Completion Date :

Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm Decitabine 20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.	Drug: Decitabine 20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles. Other Names: Dacogen

Arm

Intervention/Treatment

Experimental: Single Arm

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

Drug: Decitabine

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

Other Names:

Dacogen

Outcome Measures

Primary Outcome Measures

Reduction in pre-transplant disease burden [2 years]

Secondary Outcome Measures

Proportion of patients with suitable donor able to proceed to an allogeneic HCT [2 years]
Non-relapse mortality [3 years]
Time to neutrophil engraftment [2 years]
Overall survival survival [3 years]
Disease free survival [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
Therapy-related MDS with IPSS Int-2 and above or WPSS 3
Acceptable cardiac function MUGA or Echocardiography left ventricular ejection fraction of 40% and above
Acceptable lung function: FEV1>70% predicted, DLCO>60% predicted
Acceptable renal function: CCT > 50ml/min
Acceptable liver function: abnormalities in bilirubin or transaminases not > 2times upper limit of normal
Performance status of ECOG 2 or HCT-specific Comorbidity Index < 3

Exclusion Criteria:

Any co-morbidity other than MDS which limits life-expectancy to <3mth
Diagnosis of other active cancer other than squamous cell carcinoma, basal cell carcinoma or carcinoma-in-situ 1 or 2 of the cervix
Presence of active infections not under control
Receipt of 5-azacytidine or other induction chemotherapy for MDS/AML
Patients not keen to explore allogeneic HCT as part of curative treatment plan
Pregnancy