Safety and Efficacy of 72-hour and 120-hour Infusion of Rigosertib in Acute Myeloid Leukemia (AML) and Acute Lymphoid Leukemia (ALL)
For patients with leukemia who have not responded to or have progressed after an initial response to standard therapy, therapeutic options are limited. Although responses to standard regimens do occur, durable remissions are achieved infrequently and current regimens are not curative in the majority of patients. Identification of active agents in patients with relapsed Acute Myeloid Leukemia (AML) ultimately affords the potential for use upfront as a component of induction regimens that may translate to improved outcome. Therefore, development of new agents is of critical importance. This study will look at a new, investigational agent, ON 01910.Na, to determine if it has the potential to help Patients with AML and Acute Lymphocytic Leukemia (ALL) and transformed Myeloproliferative Neoplasms.
Acute Myelocytic Leukemia
Acute Lymphocytic Leukemia
Chronic Myeloid Leukemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1/2, Single Arm Study To Assess the Efficacy and Safety of Rigosertib (ON 01910.Na) Administered as 72-Hour and 120-Hour Continuous Intravenous Infusions Every Other Week for Two Cycles Then as Twice Daily Oral Capsules Given Continuously in Patients With Relapsed/Refractory Acute Myeloid or Lymphocytic Leukemia or Transformed Myeloproliferative Neoplasms|
- Dose Limiting Toxicity (DLT) [ Time Frame: Up to 8 months ] [ Designated as safety issue: Yes ]
DLT: adverse event possibly related that is:
- Grade ≥ 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, esophagitis/dysphagia
- Grade ≥ 3 nausea and vomiting uncontrolled by antiemetics; grade ≥ 3 diarrhea uncontrolled by antidiarrheal agents; grade ≥ 3 drug-induced fever uncontrolled by antipyretics; grade ≥3 metabolic abnormalities that are not controlled by optimal supportive care measures
- Grade ≥ 3 stomatitis and/or esophagitis/dysphagia lasting > 3 days
- Marrow cellularity <5% on day 42 or later (6 weeks) from start of therapy without evidence of leukemia
- Change in bone marrow blast cell and peripheral blood counts at 5, 13 and 25 weeks [ Time Frame: 18 months ] [ Designated as safety issue: No ]Determine the clinical response rate (complete or partial remission) according to response criteria in patients with relapsed/refractory acute myeloid or lymphocytic leukemia (1 Cheson BD, Bennett JM, Kopecky KJ, et al. Revised Recommendations of the International Working Group for Diagnosis, Standardization or Response Criteria, Treatment Outcomes and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. JCO 21:4642, 2003).
- Concentration of ON 01910.Na in plasma [ Time Frame: Week 1 and Week 3 ] [ Designated as safety issue: No ]Blood samples to determine concentration of rigosertib in plasma will be collected at 6 hours after the start of the second 24-hour infusion (Day 2) at Weeks 1 and 3.
|Study Start Date:||July 2010|
|Estimated Study Completion Date:||January 2014|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Patients will receive 2400 mg dose of rigosertib as a intravenous continuous infusion over 24 hours for 72 to 120 consecutive hours every 2 weeks for the first 4 weeks then will receive oral rigosertib at a 560 mg twice-daily dose as capsules taken continuously.
The dose of rigosertib will be 2400 mg/24h as an intravenous continuous infusion over 72 or 120 hours every 2 weeks for 2 cycles then as oral capsules administered at a dose of 560 mg twice daily on a continuous basis.
Other Name: rigosertib sodium
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|United States, Texas|
|University of Texas M. D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jorge Cortes, MD||M.D. Anderson Cancer Center|