Use of Ribavirin and Low Dose Ara-C to Treat Acute Myeloid Leukemia
|Acute Myeloid Leukemia||Drug: Ribavirin Drug: Cytarabine arabinoside||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Ribavirin and Low-dose Cytarabine Arabinoside (Ara-C) in Acute Myeloid Leukemia (AML) M4 and M5 Subtypes, and AML With High eIF4E Expression|
- Recommended Phase II Dose (RP2D) of Ribavirin When Given in Combination With Low-dose Ara-C [ Time Frame: 56 days ]This 3+3 designed aimed to determine recommended phase II dose (RP2D) based on pharmacokinetics (PK) and maximum tolerated dose (MTD). For the dose to be selected, a target steady state level of ribavirin 20 uM was needed for all patients and no more than 1 of 6 patients could have had dose limiting toxicity at that dose.
- Overall Response Rate [ Time Frame: 2-3 years ]Overall response rate comprises complete response (<5% blasts in the bone marrow, and in the peripheral blood Hgb more than or equal to 100 g/L, platelets more than or equal to 100x10-9/L, and neutrophils more than or equal to 1x10-9/L), partial response (5 to 25% blasts in the bone marrow and same peripheral blood parameters) and blast response (a greater than 50% decrease in bone marrow blast count and 2 log reduction in peripheral blood blast count, sustained for at least 28 days).
- Complete Response Rate [ Time Frame: 2-3 years ]Defined as <5% blasts in the bone marrow and a hgb 100 g/L, platelets 100,000/uL, neutrophils 1000/uL.
- Partial Response [ Time Frame: 2-3 years ]Partial response was defined as 5 to 25% blasts in the bone marrow and Hgb >100g/L, platelets >100,000/ul and neutrophils >1000/ul.
- Blast Response [ Time Frame: 2-3 years ]Blast response was defined as a greater than 50% decrease in bone marrow blast count and 2 log reduction in peripheral blood blast count, sustained for at least 28 days.
|Study Start Date:||January 2010|
|Study Completion Date:||January 2015|
|Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Ribavirin-Cytarabine arabinoside
Ribavirin will be given orally bid according to a dose escalation scheme daily for 28 days of a 28 day cycle Cytarabine arabinoside will be given 20 mg sc bid days 1 to 10 of a 28 day cycle
Dose level 1 = 1000 mg po BID/ Dose level 2 = 1400 mg po BID/ Dose level 3 = 1800 mg po BIDDrug: Cytarabine arabinoside
Previous cohorts at 20 mg bid days 1 to 10 of every 28 day cycle. Dosage modified to 10 mg bid days 1 to 10 of every 28 day cycle for more recent cohorts.
Other Name: Ara-C
In the Phase I portion of this study, we will determine the maximum tolerated dose and recommended phase II dose (RP2D) of ribavirin and low-dose ara-C. The primary objective of the Phase II portion of the study is to determine the overall response rate, including the complete remission (CR), complete remission with incomplete blood count recovery (CRi), partial remission (PR) or blast response (BR), to therapy with ribavirin and low dose ara-C at the RP2D.
STUDY DESIGN AND DURATION
This is a multicentre, open-label, single arm Phase I/II study of oral ribavirin and low-dose ara-C for patients with AML M4/M5 or AML with high expression of eIF4E, who have relapsed or refractory disease, or who are not suitable candidates for induction chemotherapy. This study will determine the recommended phase II dose and will evaluate efficacy. Correlative studies will be included to assess relevant molecular targets.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01056523
|Jewish General Hospital|
|Montreal, Quebec, Canada, H3T 1E2|
|Principal Investigator:||Sarit Assouline, MD||Jewish General Hospital, McGill University|
|Study Director:||Katherine Borden, PhD||Université de Montréal|