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

Acute Myelocytic Leukemia Clinical Trial

— Borden-001  

Official title:

A Phase II Study of Ribavirin in Refractory of Relapsed Acute Myelocytic Leukemia M4 and M5 Subtypes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00559091
• Other study ID #: CR0620KB
• Secondary ID: REC:06-112
• Status: Completed
• Phase: Phase 2
• Start date: April 2007
• Est. completion date: February 2010

Study information

• Verified date: December 2022
• Source: Jewish General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myelocytic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.

Locations

Country	Name	City	State
Canada	McMaster Hospital	Hamilton	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Jewish General Hospital	The Leukemia and Lymphoma Society

Country where clinical trial is conducted

Canada, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure: Overall response rate		6 months
Secondary	Measure: Safety and tolerability, correlative studies		6 months

External Links

•   Click here for more information about the study.