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

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.

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Decitabine

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

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction in pre-transplant disease burden	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	3 years
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

Collaborators and Investigators

• Sponsor: Singapore General Hospital
• Collaborators: Johnson & Johnson
• Investigators: Principal Investigator: Aloysius Ho, Singapore General Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: November 30, 2010
• First Submitted That Met QC Criteria: April 10, 2011
• First Posted (Estimate): April 12, 2011

Study Record Updates

• Last Update Posted (Estimate): June 17, 2014
• Last Update Submitted That Met QC Criteria: June 16, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Decitabine; MDS, myelodysplastic syndrome; prospective open label, phaseII; Allogeneic Hematopoietic cell transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: Decitabine01