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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01333449
• Other study ID #: Decitabine01
• Status: Terminated
• Phase: Phase 2
• First received: November 30, 2010
• Last updated: June 16, 2014
• Start date: July 2010
• Est. completion date: August 2013

Study information

• Verified date: June 2014
• Source: Singapore General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Health Sciences Authority
• Study type: Interventional

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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 65 Years

Eligibility

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

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

Intervention

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

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
Singapore General Hospital	Johnson & Johnson

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in pre-transplant disease burden		2 years	No
Secondary	Proportion of patients with suitable donor able to proceed to an allogeneic HCT		2 years	No
Secondary	Non-relapse mortality		3 years	No
Secondary	Time to neutrophil engraftment		2 years	No
Secondary	Overall survival survival		3 years	No
Secondary	Disease free survival		3 years	No