- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00559091
A Study of Ribavirin to Treat M4 and M5 Acute Myelocytic Leukemia (Borden-001)
A Phase II Study of Ribavirin in Refractory of Relapsed Acute Myelocytic Leukemia M4 and M5 Subtypes
Study Overview
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 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada, L8N 3Z5
- McMaster Hospital
-
-
Quebec
-
Montreal, Quebec, Canada, H1T 2M4
- Maisonneuve-Rosemont Hospital
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Montreal, Quebec, Canada, H4T 1E2
- Jewish General Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: I
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Measure: Overall response rate
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Measure: Safety and tolerability, correlative studies
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Kathy Borden, PhD, Université de Montréal
Publications and helpful links
General 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. doi: 10.1128/MCB.23.24.8992-9002.2003.
- 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.
- 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.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CR0620KB
- REC:06-112
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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