A Pilot Investigator-Initiated Study of Ribavirin in Indolent Follicular Lymphoma and Mantle Cell Lymphoma

Study Overview
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Brief Summary
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This is a A Pilot Investigator-Initiated Study of Ribavirin in Indolent Follicular Lymphoma and Mantle Cell Lymphoma

Detailed Description
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This clinical trial is for men and women ages 18 and older with follicular lymphoma with detectable BCL2-t or mantle cell lymphoma with presence of cyclin D1 overexpression (can be newly diagnosed or relapsed). The objective of this study is to assess the possibility of treating follicular lymphoma and mantle cell lymphoma patients with ribavirin and using cell free DNA (cfDNA) for BCL2-t and cyclin D1 extracted from peripheral blood to measure treatment effect. Clinical trials of ribavirin have been conducted in relapsed and refractory acute myeloid leukemia (AML). Ribavirin, an antiviral agent with established doses, has resulted in the regression of the tumor. Ribavirin 1000 mg will be administered orally twice daily continuously for 28-day cycles. Patients will be followed for up to 7 months. Will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.

Official Title
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A Pilot Investigator-Initiated Study of Ribavirin in Indolent Follicular Lymphoma and Mantle Cell Lymphoma

Conditions
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Follicular Lymphoma, Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of histologically confirmed follicular lymphoma with detectable BCL2-t or mantle cell lymphoma with presence of cyclin D1 overexpression (can be newly diagnosed or relapsed) Measurable disease (At least one tumor mass > 1 cm in diameter) Low tumor burden: No individual masses larger than 6 cm in diameter No more than three masses larger than 3 cm in diameter No lymphoma-related symptoms The treating physician does not feel that treatment with chemotherapy is indicated ECOG performance status of 0-2 Adequate bone marrow and end organ function: i. ANC≥1500/mm3, hemoglobin≥10 g/dL, platelet≥100/mm3 ii. CrCL≥50 mL/min by Cockcroff Gault calculation Exclusion Criteria: Indication for treatment of lymphoma including large tumor burden or symptomatic disease Pregnancy or men whose female partners are pregnant Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment) Significant or unstable cardiac disease Hemoglobinopathy (thalassemia or sickle cell disease)

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: Ribavirin<br>Ribavirin 1000 mg will be administered orally twice daily continuously in 28 day cycles for up to 6 cycles. | Drug: Ribavirin<br>* Ribavirin is FDA-approved oral medication for antiviral indications. Ribavirin will be obtained commercially for this trial. Treatment will be administered on an outpatient basis. Ribavirin should be administered with food.<br>* Other names: Copegus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who receive treatment for at least 3 months, have peripheral blood samples collected at baseline and monthly while on treatment, and have levels of BCL-t or cyclin D1, respectively, obtained from their peripheral blood samples | Feasibility will be measured by the number of subjects who receive ribavirin for at least 3 months, have peripheral blood samples collected at baseline and monthly while on treatment, and have levels of BCL-t and cyclin D1, respectively, obtained from their peripheral blood samples. The intervention will be deemed feasible if all three criteria are met in 10 out of 15 subjects. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related Serious Adverse Events as assessed by the CTCAE v4.0 | Tolerability of ribavirin in FL and MCL will be assessed by the number of Number of participants with treatment-related Serious Adverse Events as assessed by the CTCAE v4.0. | 18 months | 
| Number of participants who achieve a response to ribavirin treatment based on PET/CT or CT | Response rate will be assessed by the number of participants who achieve a response to ribavirin treatment based on PET/CT or CT at baseline and within 4 weeks after completion of treatment. International working group criteria will be used for response assessment based on imaging done at baseline and 2-4 weeks after completion of therapy. The total number of participants who achieve a response will be assessed after the last patient has their response assessed after completion of therapy. | 18 months | 
| Average change in BCL2-t or Cyclin D1 cfDNA levels | Correlatives will be assessed by the change in BCL2-t or Cyclin D1 cfDNA levels. This will be correlated with response rates based on imaging. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ribavirin, Follicular Lymphoma, Mantle Cell Lymphoma, Lymphoma, Non-Hodgkin lymphoma, Indolent Lymphoma