Overview

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

Status:
Terminated

Trial end date:
2013-08-01

Target enrollment:
0

Participant gender:
All

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.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Singapore General Hospital

Collaborator:

Johnson & Johnson

Treatments:

Azacitidine
Decitabine

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