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

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

Study Overview

• Status: Terminated
• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Ribavirin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. No individual masses larger than 6 cm in diameter
  2. No more than three masses larger than 3 cm in diameter
  3. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ribavirin; Ribavirin 1000 mg will be administered orally twice daily continuously in 28 day cycles for up to 6 cycles.	Drug: Ribavirin; 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.; Other Names: Copegus; Rebetol; Virazole

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Sarah Rutherford, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 26, 2018
• Primary Completion (ACTUAL): July 22, 2020
• Study Completion (ACTUAL): July 22, 2020

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: July 11, 2018
• First Posted (ACTUAL): July 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 27, 2021
• Last Update Submitted That Met QC Criteria: September 20, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Lymphoma; Follicular Lymphoma; Ribavirin; Mantle Cell Lymphoma; Non-Hodgkin lymphoma; Indolent Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: 1709018594

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No