Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Ribavirin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

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 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.

Cytarabine arabinoside

Sarit Assouline, MD

Katherine Borden, PhD

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.

Use of Ribavirin and Low Dose Ara-C to Treat Acute Myeloid Leukemia

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

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 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).

Defined as \<5% blasts in the bone marrow and a hgb 100 g/L, platelets 100,000/uL, neutrophils 1000/uL.

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 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.

The Leukemia and Lymphoma Society

Jewish General Hospital

Principal Investigator

Ribavirin: Dose level 1 = 1000 mg po BID/ Dose level 2 = 1400 mg po BID/ Dose level 3 = 1800 mg po BID

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.

Ribavirin-Cytarabine

Dose level 1 = 1000 mg po BID/ Dose level 2 = 1400 mg po BID/ Dose level 3 = 1800 mg po BID Drug: 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.

Ribavirin and Cytarabine

Age, Continuous

Sex: Female, Male

FAB - French American British leukemia classification

FAB subtype

Dr. Assouline

Ribavirin po bid for 28 days

cytarabine arabinoside sc bid for 10 days

Recommended Phase II Dose (RP2D) of Ribavirin When Given in Combination With Low-dose Ara-C

Patients with relapsed or refractory AML or elderly untreated AML with FAB subtype M4/M5 or overexpressing eIF4E were treated with ribavirin and cytarabine arabinoside according to a 3+3 dose escalation scheme

Only patients treated for 28 days or more were evaluable for response.

Overall Response Rate

Only patients treated for at least 28 days were evaluable for response.

Complete Response Rate

Only patients treated for 28 days or more were assessed for response.

Partial Response

Blast Response

Ribavirin 1000 mg po bid x 28 days, cytarabine arabinoside 20 mg sc bid days 1 to 10

Dose Level 1

Ribavirin 1400 mg po bid x 28 days, cytarabine arabinoside 20 mg sc bid days 1 to 10

Dose Level 2

Ribavirin 1800 mg po bid x 28 days, cytarabine arabinoside 20 mg sc bid days 1 to 10

Dose Level 3

Ribavirin 2200 mg po bid x 28 days, cytarabine arabinoside 20 mg sc bid days 1 to 10

Dose Level 4

Ribavirin 1000 mg po bid x 28 days, cytarabine arabinoside 10 mg sc bid days 1 to 10

Dose Level 5

Ribavirin 1400 mg po bid x 28 days, cytarabine arabinoside 10 mg sc bid days 1 to 10

Dose Level 6

Ribavirin 1800 mg po bid x 28 days, cytarabine arabinoside 10 mg sc bid days 1 to 10

Spots Global Cancer Trial Database for cytarabine arabinoside