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

Primary Purpose

Myelodysplastic Syndrome

Status
Terminated
Phase
Phase 2
Locations
Singapore
Study Type
Interventional
Intervention
Decitabine
Sponsored by
Singapore General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring Decitabine, MDS, myelodysplastic syndrome, prospective open label, phaseII, Allogeneic Hematopoietic cell transplant

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Singapore General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm

Arm Description

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

Outcomes

Primary Outcome Measures

Reduction in pre-transplant disease burden

Secondary Outcome Measures

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

Full Information

First Posted
November 30, 2010
Last Updated
June 16, 2014
Sponsor
Singapore General Hospital
Collaborators
Johnson & Johnson
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1. Study Identification

Unique Protocol Identification Number
NCT01333449
Brief Title
Study of Decitabine Induction Prior to Allogeneic Hematopoietic Cell Transplant in Newly Diagnosed MDS Patients
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 Type
Interventional

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Terminated
Why Stopped
Poor subject accrual
Study Start Date
July 2010 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Singapore General Hospital
Collaborators
Johnson & Johnson

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome
Keywords
Decitabine, MDS, myelodysplastic syndrome, prospective open label, phaseII, Allogeneic Hematopoietic cell transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Arm
Arm Type
Experimental
Arm Description
Decitabine 20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
Dacogen
Intervention Description
20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.
Primary Outcome Measure Information:
Title
Reduction in pre-transplant disease burden
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Proportion of patients with suitable donor able to proceed to an allogeneic HCT
Time Frame
2 years
Title
Non-relapse mortality
Time Frame
3 years
Title
Time to neutrophil engraftment
Time Frame
2 years
Title
Overall survival survival
Time Frame
3 years
Title
Disease free survival
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aloysius Ho
Organizational Affiliation
Singapore General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
169608
Country
Singapore

12. IPD Sharing Statement

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

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