A Study of Ribavirin to Treat M4 and M5 Acute Myelocytic Leukemia (Borden-001)
Primary Purpose
Acute Myelocytic Leukemia
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myelocytic Leukemia focused on measuring AML, Acute myelocytic leukemia, leukemia, relapsed, refractory, M4, M5
Eligibility 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.
Sites / Locations
- McMaster Hospital
- Maisonneuve-Rosemont Hospital
- Jewish General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
I
Arm Description
Ribavirin
Outcomes
Primary Outcome Measures
Measure: Overall response rate
Secondary Outcome Measures
Measure: Safety and tolerability, correlative studies
Full Information
NCT ID
NCT00559091
First Posted
November 15, 2007
Last Updated
December 20, 2022
Sponsor
Jewish General Hospital
Collaborators
The Leukemia and Lymphoma Society
1. Study Identification
Unique Protocol Identification Number
NCT00559091
Brief Title
A Study of Ribavirin to Treat M4 and M5 Acute Myelocytic Leukemia
Acronym
Borden-001
Official Title
A Phase II Study of Ribavirin in Refractory of Relapsed Acute Myelocytic Leukemia M4 and M5 Subtypes
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Jewish General Hospital
Collaborators
The Leukemia and Lymphoma Society
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelocytic Leukemia
Keywords
AML, Acute myelocytic leukemia, leukemia, relapsed, refractory, M4, M5
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
I
Arm Type
Experimental
Arm Description
Ribavirin
Intervention Type
Drug
Intervention Name(s)
ribavirin
Other Intervention Name(s)
Ribasphere (Three Rivers Pharmaceuticals)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Measure: Overall response rate
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Measure: Safety and tolerability, correlative studies
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarit Assouline, MD
Organizational Affiliation
Jewish General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kathy Borden, PhD
Organizational Affiliation
Université de Montréal
Official's Role
Study Director
Facility Information:
Facility Name
McMaster Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Maisonneuve-Rosemont Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4T 1E2
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
14645512
Citation
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.
Results Reference
background
PubMed Identifier
10216944
Citation
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.
Results Reference
background
PubMed Identifier
15601771
Citation
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.
Results Reference
background
PubMed Identifier
19433856
Citation
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.
Results Reference
background
Links:
URL
http://www.ribatrial.com
Description
Click here for more information about the study.
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A Study of Ribavirin to Treat M4 and M5 Acute Myelocytic Leukemia
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