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

Early Phase 1

Terminated

• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma
• Interventions: Drug: Ribavirin

• Registration Number: NCT03585725
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

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

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 Timeline

• Study First Submitted: 2018-05-25
• Study First Submitted QC: 2018-07-11
• Study First Posted: 2018-07-13
• Study Start: 2018-09-26
• Primary Completion: 2020-07-22
• Study Completion: 2020-07-22
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-20
• Last Update Posted: 2021-09-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ribavirin	Ribavirin	Ribavirin 1000 mg will be administered orally twice daily continuously in 28 day cycles for up to 6 cycles.

Primary Outcome Measures

Name	Time	Method
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	18 months	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.

Secondary Outcome Measures

Name	Time	Method
Number of participants with treatment-related Serious Adverse Events as assessed by the CTCAE v4.0	18 months	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.
Number of participants who achieve a response to ribavirin treatment based on PET/CT or CT	18 months	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.
Average change in BCL2-t or Cyclin D1 cfDNA levels	18 months	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.

Trial Locations

Locations (1)

Weill Cornell Medicine; 🇺🇸 New York, New York, United States