A Study of Ribavirin to Treat M4 and M5 Acute Myelocytic Leukemia

NCT ID: NCT00559091

Last Updated: 2022-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-30

Study Completion Date

2010-02-28

Brief Summary

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The purpose of this study is to determine if ribavirin (a drug commonly used to treat hepatitis C) also has activity in the treatment of patients with refractory or relapsed acute myeloid leukemia (AML) of the M4 and M5 subtype.

Detailed Description

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The eukaryotic translation initiation factor eIF4E is dysregulated in many human malignancies, including a subset of myeloid leukemia (M4/M5 AML and blast crisis CML). eIF4E overexpression leads to oncogenic transformation. Ribavirin impedes eIF4E mediated transformation in vitro, in primary human specimens and in animal models.

While ribavirin has been used extensively for the treatment of viral hepatitis C and its safety profile has been well defined, it has never been used in patients with AML. This study will establish the efficacy and safety of ribavirin in M4/M5 AML patients. In addition, this study will also include correlative studies to determine the effect of ribavirin on eIF4E activity and eIF4E related pathways in M4/M5 AML patients.

Conditions

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Acute Myelocytic Leukemia

Keywords

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AML Acute myelocytic leukemia leukemia relapsed refractory M4 M5

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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I

Ribavirin

Group Type EXPERIMENTAL

ribavirin

Intervention Type DRUG

Ribavirin will be administered orally, twice daily, in the morning and evening with food. The dose selected is 400 mg AM and 600 mg PM. Intrapatient dose escalations can also be performed in defined circumstances. The maximal dose administered will be 1000 mg AM and 1000 mg PM.

Interventions

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ribavirin

Ribavirin will be administered orally, twice daily, in the morning and evening with food. The dose selected is 400 mg AM and 600 mg PM. Intrapatient dose escalations can also be performed in defined circumstances. The maximal dose administered will be 1000 mg AM and 1000 mg PM.

Intervention Type DRUG

Other Intervention Names

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Ribasphere (Three Rivers Pharmaceuticals)

Eligibility Criteria

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Inclusion Criteria

* A diagnosis of acute myeloid leukemia (AML), either M4 or M5 subtype de novo or resulting from a transformation from MDS or a myeloproliferative disorder.
* Patients with AML who (a) have failed primary therapy -defined as failing two induction chemotherapies, (b) have relapsed or (c) are not suitable for intensive induction chemotherapy will be eligible. OR
* Patients with AML blast crisis from CML if they are not suitable candidates for intensive induction chemotherapy or have failed imatinib mesylate OR
* Patients with secondary AML after MDS if they are not suitable candidates for intensive induction chemotherapy.
* ECOG 0,1,2, or 3
* Life expectancy \> 12 weeks.
* Adequate renal and hepatic function

Exclusion Criteria

* Uncontrolled central nervous system involvement by AML
* Active cardiovascular disease as defined by NYHA class III-IV categorization.
* Intercurrent illness or medical condition precluding safe administration of ribavirin.
* Received any previous therapy within 28 days prior to study entry.Hydrea is permitted but must be stopped 7 days prior to starting study drug.
* Known infection with HIV.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Leukemia and Lymphoma Society

OTHER

Sponsor Role collaborator

Jewish General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Sarit Assouline

Associate Professor, Department of Oncology, McGill University

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sarit Assouline, MD

Role: PRINCIPAL_INVESTIGATOR

Jewish General Hospital

Kathy Borden, PhD

Role: STUDY_DIRECTOR

Université de Montréal

Locations

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McMaster Hospital

Hamilton, Ontario, Canada

Site Status

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Countries

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Canada

References

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Topisirovic I, Guzman ML, McConnell MJ, Licht JD, Culjkovic B, Neering SJ, Jordan CT, Borden KL. Aberrant eukaryotic translation initiation factor 4E-dependent mRNA transport impedes hematopoietic differentiation and contributes to leukemogenesis. Mol Cell Biol. 2003 Dec;23(24):8992-9002. doi: 10.1128/MCB.23.24.8992-9002.2003.

Reference Type BACKGROUND
PMID: 14645512 (View on PubMed)

De Benedetti A, Harris AL. eIF4E expression in tumors: its possible role in progression of malignancies. Int J Biochem Cell Biol. 1999 Jan;31(1):59-72. doi: 10.1016/s1357-2725(98)00132-0.

Reference Type BACKGROUND
PMID: 10216944 (View on PubMed)

Kentsis A, Topisirovic I, Culjkovic B, Shao L, Borden KL. Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18105-10. doi: 10.1073/pnas.0406927102. Epub 2004 Dec 15.

Reference Type BACKGROUND
PMID: 15601771 (View on PubMed)

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)

Related Links

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http://www.ribatrial.com

Click here for more information about the study.

Other Identifiers

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REC:06-112

Identifier Type: -

Identifier Source: secondary_id

CR0620KB

Identifier Type: -

Identifier Source: org_study_id