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

NCT01333449 | Terminated Phase 2 DMC

• 1 other identifier: Decitabine01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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:

1. 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. 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.

Conditions

Myelodysplastic Syndrome

Keywords

Decitabine; MDS, myelodysplastic syndrome; prospective open label, phaseII; Allogeneic Hematopoietic cell transplant

Outcome Measures

Primary Outcomes (1)

• Reduction in pre-transplant disease burden

  2 years

Secondary Outcomes (5)

• 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

Study Arms (1)

Single Arm

EXPERIMENTAL

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

Drug: Decitabine

Interventions

Decitabine DRUG

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

Also known as: Dacogen

Single Arm

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Singapore General Hospital: lead
• Johnson & Johnson: collaborator

Study Sites (1)

Singapore General Hospital

Singapore, Singapore, 169608, Singapore

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts

Interventions

Decitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Aloysius Ho

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2010
• First Posted: April 12, 2011
• Study Start: July 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: June 17, 2014

Record last verified: 2014-06

Locations

SG (1)