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

NCT ID: NCT01056523

Last Updated: 2023-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2015-01-31

Brief Summary

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.

Detailed Description

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Ribavirin

Intervention Type: DRUG

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

Cytarabine arabinoside

Intervention Type: DRUG

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.

Interventions

Ribavirin

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Ara-C

Eligibility Criteria

Inclusion Criteria

• The following patients with acute myeloid leukemia (AML) are eligible:

• De novo AML M4 or M5 FAB subtype or high eIF4E.
• Secondary AML after a myelodysplastic syndrome (MDS) or a myeloproliferative disorder (not chronic myelogenous leukemia), if M4 or M5 FAB subtype or high eIF4E.
• Therapy-related AML if M4 or M5 FAB subtype or high eIF4E.
• CML blast crisis if they have failed imatinib and at least one other tyrosine kinase inhibitor.
• All patients must have failed primary therapy (defined as two induction chemotherapies), have relapsed, or are not suitable candidates for intensive induction chemotherapy.
• Patients who have a dry aspirate or extramedullary disease only are eligible for this study if they have a pre-treatment marrow or tissue biopsy demonstrating AML M4 or M5 subtype or high eIF4E expression.
• ECOG performance status 0, 1, 2 or 3.
• Life expectancy > 4 weeks.
• Age is > 18 years.
• Female patients of childbearing potential must have a negative serum (beta-HCG) pregnancy test within 14 days of starting protocol and must not be breastfeeding. Men and women of childbearing potential must agree to use an effective means of contraception throughout the study and for at least 30 days after completion of protocol.
• Adequate renal and hepatic function: serum creatinine < 1.5 x ULN; AST or ALT < 2.5 x ULN (or < 5 x ULN if liver involvement with leukemia); serum bilirubin < 1.5 x ULN.
• Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
• Accessible for treatment and follow up.

Exclusion Criteria

• Uncontrolled central nervous system involvement by AML.
• Active cardiovascular disease as defined by New York Heart Association (NYHA) class III-IV categorization.
• Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment or required follow-up.
• Received any previous therapy for AML within 28 days prior to the study entry. Hydrea is permitted for the treatment of leukocytosis but must be stopped within 7 days of starting low dose ara-C and ribavirin.
• Female patients who are pregnant or breastfeeding.
• Concurrent treatment with other anti-cancer therapy.
• Known infection with HIV.
• History of other malignancy. Subjects who have been disease-free for 2 year or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
• FAB AML M1, 2, 6, 7 will be excluded if they do not have high eIF4E expression. AML M3 is always excluded.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Leukemia and Lymphoma Society

OTHER

Sponsor Role: collaborator

Jewish General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sarit Assouline

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sarit Assouline, MD

Role: PRINCIPAL_INVESTIGATOR

Jewish General Hospital, McGill University

Katherine Borden, PhD

Role: STUDY_DIRECTOR

Université de Montréal

Locations

Jewish General Hospital

Montreal, Quebec, Canada

Countries

Canada

References

Assouline S, Culjkovic B, Cocolakis E, Rousseau C, Beslu N, Amri A, Caplan S, Leber B, Roy DC, Miller WH Jr, Borden KL. Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): a proof-of-principle clinical trial with ribavirin. Blood. 2009 Jul 9;114(2):257-60. doi: 10.1182/blood-2009-02-205153. Epub 2009 May 11.

Reference Type: BACKGROUND

PMID: 19433856 (View on PubMed)

Assouline S, Culjkovic-Kraljacic B, Bergeron J, Caplan S, Cocolakis E, Lambert C, Lau CJ, Zahreddine HA, Miller WH Jr, Borden KL. A phase I trial of ribavirin and low-dose cytarabine for the treatment of relapsed and refractory acute myeloid leukemia with elevated eIF4E. Haematologica. 2015 Jan;100(1):e7-9. doi: 10.3324/haematol.2014.111245. Epub 2014 Nov 25. No abstract available.

Reference Type: RESULT

PMID: 25425688 (View on PubMed)

Other Identifiers

Ribavirin-002

Identifier Type: -

Identifier Source: org_study_id