Borden-001: A Study of Ribavirin to Treat M4 and M5 Acute Myelocytic Leukemia

Sponsor

Jewish General Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00559091

Collaborator

The Leukemia and Lymphoma Society (Other)

Enrollment

Locations

Arm

34.1

Duration (Months)

8.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelocytic Leukemia	Drug: ribavirin	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2007

Actual Primary Completion Date :

Feb 1, 2010

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I 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. Other Names: Ribasphere (Three Rivers Pharmaceuticals)

Arm

Intervention/Treatment

Experimental: I

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.

Other Names:

Ribasphere (Three Rivers Pharmaceuticals)

Outcome Measures

Primary Outcome Measures

Measure: Overall response rate [6 months]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	McMaster Hospital	Hamilton	Ontario	Canada	L8N 3Z5
2	Maisonneuve-Rosemont Hospital	Montreal	Quebec	Canada	H1T 2M4
3	Jewish General Hospital	Montreal	Quebec	Canada	H4T 1E2