A Study of Ribavirin to Treat M4 and M5 Acute Myelocytic Leukemia - Full Text View

Sponsor:	Jewish General Hospital
Collaborator:	The Leukemia and Lymphoma Society
Information provided by:	Jewish General Hospital
ClinicalTrials.gov Identifier:	NCT00559091

Purpose

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.

Condition	Intervention	Phase
Acute Myelocytic Leukemia	Drug: ribavirin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Study of Ribavirin in Refractory of Relapsed Acute Myelocytic Leukemia M4 and M5 Subtypes

Resource links provided by NLM:

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Ribavirin

U.S. FDA Resources

Further study details as provided by Jewish General Hospital:

Primary Outcome Measures:

Measure: Overall response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measure: Safety and tolerability, correlative studies [ Time Frame: 6 months ]

Estimated Enrollment:	25
Study Start Date:	April 2007
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
I: Experimental Ribavirin	Drug: 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.

Detailed Description:

The eukaryotic translation initiation factor eIF4E is dysregulated in many human malignancies, including a subset of myeloid leukemia (M4/M5 AML and blast crisis CLL). 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00559091

Contacts

Contact: Caroline Rousseau, PhD	514-340-8222 ext 4599	crousseau@ldi.jgh.mcgill.ca
Contact: Eftihia Cocolakis, PhD	514-340-8222 ext 3628	ecocolakis@jgh.mcgill.ca

Locations

Canada, Ontario
McMaster Hospital	Recruiting
Hamilton, Ontario, Canada, L8N 3Z5
Contact: DeGelder Tammy 905-521-2100 ext 73435 Tammy.DeGelder@jcc.hhsc.ca
Principal Investigator: Brian Leber, MD
Canada, Quebec
Jewish General Hospital	Recruiting
Montreal, Quebec, Canada, H4T 1E2
Contact: Caroline Rousseau, PhD 514-340-8222 ext 4599 crousseau@ldi.jgh.mcgill.ca
Contact: Eftihia Cocolakis, PhD 514-340-8222 ext 3628 ecocolakis@jgh.mcgill.ca
Principal Investigator: Sarit Assouline, MD
Maisonneuve-Rosemont Hospital	Recruiting
Montreal, Quebec, Canada, H1T 2M4
Principal Investigator: Denis-Claude Roy, MD

Sponsors and Collaborators

Jewish General Hospital

The Leukemia and Lymphoma Society

Investigators

Principal Investigator:	Sarit Assouline, MD	Jewish General Hospital
Study Director:	Kathy Borden, PhD	University of Montreal

More Information

Additional Information:

Click here for more information about the study. This link exits the ClinicalTrials.gov site

Publications:

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.

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. Review.

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. Epub 2004 Dec 15.

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 AML: a proof-of-principle clinical trial with ribavirin. Blood. 2009 May 11; [Epub ahead of print]

Responsible Party:	Jewish General Hospital, McGill University ( Dr. Sarit Assouline / Associate Director, Clinical Research Unit )
Study ID Numbers:	CR0620KB, REC:06-112
Study First Received:	November 15, 2007
Last Updated:	September 23, 2009
ClinicalTrials.gov Identifier:	NCT00559091 History of Changes
Health Authority:	Canada: Health Canada

Keywords provided by Jewish General Hospital:

AML
Acute myelocytic leukemia
leukemia
relapsed

refractory
M4
M5

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia
Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action

Therapeutic Uses
Ribavirin
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Antiviral Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 30, 2009