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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Singapore General Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Johnson & Johnson
Information provided by:
Singapore General Hospital
ClinicalTrials.gov Identifier:
NCT01333449
First received: November 30, 2010
Last updated: April 10, 2011
Last verified: April 2011
History of Changes
  Purpose

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.

Condition Intervention Phase
Myelodysplastic Syndrome
 Drug: decitabine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:

Drug Information available for: Decitabine
U.S. FDA Resources

Further study details as provided by Singapore General Hospital:

Primary Outcome Measures:
  • Reduction in pre-transplant disease burden [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with suitable donor able to proceed to an allogeneic HCT [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Non-relapse mortality [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Time to neutrophil engraftment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Disease free survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: July 2010
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: decitabine
    20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.
    Other Name: dacogen
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

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01333449

Locations
Singapore
Singapore General Hospital Recruiting
Singapore, Singapore, 169608
Contact: Zhang Cailian     +65-63214627     zhang.cai.lian@sgh.com.sg    
Principal Investigator: Yvonne Loh            
Sponsors and Collaborators
Singapore General Hospital
Johnson & Johnson
Investigators
Principal Investigator: Yvonne Loh Singapore General Hospital
  More Information

No publications provided

Responsible Party: Dr Yvonne Loh, Singapore General Hospital
ClinicalTrials.gov Identifier: NCT01333449     History of Changes
Other Study ID Numbers: Decitabine01
Study First Received: November 30, 2010
Last Updated: April 10, 2011
Health Authority: Singapore: Health Sciences Authority

Keywords provided by Singapore General Hospital:
Decitabine
MDS, myelodysplastic syndrome
prospective open label, phaseII
Allogeneic Hematopoietic cell transplant

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Decitabine
 Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 21, 2013