The purpose of the study is to determine the maximum tolerated dose of ribavirin, when given in combination with low-dose ara-C and to determine if it is safe and well-tolerated in patients with acute myeloid leukemia.
Primary Objectives 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Dose level 1 = 1000 mg po BID/ Dose level 2 = 1400 mg po BID/ Dose level 3 = 1800 mg po BID
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.
Jewish General Hospital
Montreal, Quebec, Canada
Recommended Phase II Dose (RP2D) of Ribavirin When Given in Combination With Low-dose Ara-C
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.
Time frame: 56 days
Overall Response Rate
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).
Time frame: 2-3 years
Complete Response Rate
Defined as \<5% blasts in the bone marrow and a hgb 100 g/L, platelets 100,000/uL, neutrophils 1000/uL.
Time frame: 2-3 years
Partial Response
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.
Time frame: 2-3 years
Blast Response
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.
Time frame: 2-3 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.