Myelodysplastic Syndromes Clinical Trial
Official title:
Phase III MultiCenter Randomized Controlled Study to Assess Efficacy and Safety of ON 01910.Na 72-Hr Continuous IV Infusion in MDS Patients With Excess Blasts Relapsing After or Refractory to or Intolerant to Azacitidine or Decitabine
The primary objective of this study is to compare overall survival (OS) in patients receiving ON 01910.Na + best supportive care (BSC) to OS of patients receiving BSC in a population of patients with myelodysplastic syndrome (MDS) with excess blasts (5% to 30% bone marrow blasts) who have failed azacitidine or decitabine treatment. This patient population has no available therapy and a short life expectancy (approximately 4 months). The high level of bone marrow activity of ON 01910.Na documented in Phase 1 and 2 studies has the potential to delay substantially the transition of MDS to Acute Myeloid Leukemia(AML), a very significant and severe complication, which shortens survival of these MDS patients.
This is a Phase III open-label, randomized, controlled, multicenter study (up to 50 centers).
Approximately 270 patients with MDS classified as RAEB-1 and RAEB-2 using the WHO
classification and as RAEB-t and chronic myelomonocytic leukemia (CMML) using the FAB
classification who failed, became intolerant to, or progressed after treatment with
5-azacitidine or decitabine administered during the past 2 years, will be randomized in a 2:1
ratio into the following 2 treatment regimens:
- Best Supportive Care (BSC) + ON 01910.Na 1800 mg/24 hr administered as a 72-hr
continuous intravenous (CIV) infusion on Days 1, 2, and 3 of a 2-week cycle (N =
approximately 180 patients)
- BSC (N = approximately 90 patients).
Patients will be stratified at entry by bone marrow (BM) blasts (5% to 19% vs. 20% to 30%).
After completing the first eight 2-week cycles (i.e., after 16 weeks of treatment), the
frequency of further 72-hr CIV infusions will be decreased to an administration on Days 1, 2,
and 3 of a 4-week cycle.
Patients will remain treated on study until 2006 International Working Group (IWG)
progression criteria are met (i.e., 50% increase of BM blasts or worsening of cytopenias) or
until death from any cause, whichever comes first.
Patients who progress to Acute Myeloid Leukemia (AML) while on study should be offered either
standard treatment for AML or enrollment in an appropriate investigational study if they are
eligible. These treatments with their start and end dates should be documented and patient
survival time will be documented for all randomized patients.
Cross-over of BSC patients to ON 01910.Na after progression will not be allowed. However,
patients in the BSC-only group will be allowed, as medically justified, access to low-dose
cytarabine 20 mg/m2 subcutaneously (SC) once daily for the first consecutive 14 days of each
28-day cycle, up to 4 cycles, until progression or unacceptable toxicity develops. Low-dose
cytarabine will be delayed as needed until recovery of blood counts. All study participants
will be allowed, as medically justified, access to RBC and platelet transfusions and to
growth factors (erythropoietin, Filgrastim [G-CSF]). Hydroxyurea will be allowed to manage
blastic crisis with hyperleukocytosis when patients transition to leukemia.
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