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

Study Overview
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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.

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

Conditions
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Acute Myelocytic Leukemia

Intervention / Treatment
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* Drug: ribavirin


Participation Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I<br>Ribavirin | Drug: ribavirin<br>* 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.<br>* Other names: Ribasphere (Three Rivers Pharmaceuticals);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure: Overall response rate |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure: Safety and tolerability, correlative studies |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, Acute myelocytic leukemia, leukemia, relapsed, refractory, M4, M5