MRD Guided De-intensification of Bendamustine/Rituximab for Indolent Non-Hodgkin Lymphoma

NCT ID: NCT06557330

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2028-03-30

Brief Summary

This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.

Detailed Description

This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.

All patients with untreated or R/R (not previously treated with Bendamustine) iNHL (Follicular Lymphoma (Grade 1-3a2), Marginal Zone Lymphoma, Lymphoplasmacytic Lymphoma) are candidates for this trial. Patients requiring treatment per treating physician's discretion are eligible for the trial.

Patients who recently started on and received two cycles of Bendamustine at 90 mg/m2 dose with Ritxumab 375 mg/m2 are also eligible for this trial. For these patients, C2D1 BR should be no more than 14 days prior to the time of study enrollment (i.e. enrollment no later than C2D14). Patients who have received two cycles of 90mg/m2 Bendamustine dose with Rituximab 375 mg/m2 can enter the study and initiate cycle 3 once pre-screening and screening procedures have been completed.

Conditions

Lymphoma; Indolent Non-hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Single Arm

This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of Measurable Residual Disease (MRD) adapted duration of BR for untreated or R/R iNHL (indolent non-hodgkin lymphoma). All patients will receive Bendamustine 90 mg/m2 IV on Days 1-2 and Rituximab 375 mg/m2 IV(BR) on Day 1 of each cycle. Each cycle will last 28 days. On day 1 of each cycle, patients will receive Rituximab before Bendamustine, and CBC (complete blood count), CMP (comprehensive metabolic panel) will be obtained to capture any hematologic toxicities as well as clonoSEQ testing to determine MRD status. After completing Cycle 3, imaging results (with confirmatory biopsy if applicable) and the clonoSEQ MRD testing results obtained from ctDNA (blood collection) will determine whether patients will receive Cycles 5 and 6 of Bendamustine and Rituximab (BR).

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

Bendamustine will be administered as 10 minute IV infusion at 90 mg/m2 (drug dose calculation is based on treatment day weight) on days 1 and 2 for 4-6 cycles (number of cycles determined per treatment design). Subjects will be dosed every 28 days. Ondansetron 16 mg IV is given as premedication per institutional guidelines. Dose modifications will be determined based on renal and hepatic function. Subjects should be carefully monitored for infusion reactions during Bendamustine administration. If an acute infusion reaction is noted, subjects should be managed according to institutional guidelines. Doses of Bendamustine may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment based on physician discretion.

Rituximab

Intervention Type: DRUG

Rituximab will be administered as an IV infusion at 375 mg/m2 (longer for the first dose) (drug dose calculation is based of treatment day weight) on day 1 for 4-6 cycles (number of cycles determined per treatment design). Infusion rate will be determined as per institutional standards. Subjects will be dosed every 28 days. Diphenhydramine 50 mg IV and acetaminophen 650 mg are required to be given to the subjects within 30 minutes prior to Rituximab dose. There are no dose modifications recommended with Rituximab. If an acute infusion reaction is noted, subjects should be managed according to institutional guidelines. Doses of Rituximab may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment.

Interventions

Bendamustine

Bendamustine will be administered as 10 minute IV infusion at 90 mg/m2 (drug dose calculation is based on treatment day weight) on days 1 and 2 for 4-6 cycles (number of cycles determined per treatment design). Subjects will be dosed every 28 days. Ondansetron 16 mg IV is given as premedication per institutional guidelines. Dose modifications will be determined based on renal and hepatic function. Subjects should be carefully monitored for infusion reactions during Bendamustine administration. If an acute infusion reaction is noted, subjects should be managed according to institutional guidelines. Doses of Bendamustine may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment based on physician discretion.

Intervention Type: DRUG

Rituximab

Rituximab will be administered as an IV infusion at 375 mg/m2 (longer for the first dose) (drug dose calculation is based of treatment day weight) on day 1 for 4-6 cycles (number of cycles determined per treatment design). Infusion rate will be determined as per institutional standards. Subjects will be dosed every 28 days. Diphenhydramine 50 mg IV and acetaminophen 650 mg are required to be given to the subjects within 30 minutes prior to Rituximab dose. There are no dose modifications recommended with Rituximab. If an acute infusion reaction is noted, subjects should be managed according to institutional guidelines. Doses of Rituximab may be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment.

Intervention Type: DRUG

Other Intervention Names

cytostasan; belrapzo; treanda; vivimusta; riabni; Rituxan; Ruxience; Truxima; Azulfidine

Eligibility Criteria

Inclusion Criteria

Patients must have pathologically confirmed:

• indolent Non-Hodgkin Lymphoma, consistent with one of the below diagnoses:
• Follicular Lymphoma (Grade 1-3a)
• Marginal Zone Lymphoma
• Lymphoplasmacytic Lymphoma

Patient may be treatment naïve or relapsed/refractory without having received prior Bendamustine or patients recently started on Bendamustine 90 mg/m2 with Rituximab 375 mg/m2 are eligible if C2D1 BR is no more than 14 days prior to enrollment and they otherwise meet eligibility criteria

• Age > 18 years
• ECOG performance status 0-2

Patients must have normal organ and marrow function as defined below:

• Absolute Neutrophil Count >1000mm3 and Hemoglobin >8 g/dL (unless due to bone marrow involvement by lymphoma)
• Total bilirubin > 1.5x upper limit of normal (patients with Gilbert's syndrome can have total bilirubin up to 3x upper normal limit)
• Aspartate aminotransferase/ alanine aminotransferase (serum glutamic-oxaloacetic transaminase/ serum glutamic-pyruvic transaminase) < 5 times institutional normal limits
• Creatinine clearance > 30 Ml/min

Exclusion Criteria

• Radiation or systemic treatment for lymphoma within the past 28 days prior to cycle 1 day 1 of BR.
• Patients with pathologically confirmed transformed lymphoma, including diffuse large B cell lymphoma or other high grade lymphomas
• Patients on active treatment for second malignancy with the exception of endocrine therapy for non-metastatic breast cancer, hormone therapy for prostate cancer, or local treatment for non-melanoma skin cancer.
• Pregnant or breast-feeding. Refer to section 5.4 for further detail.
• Failure to identify a dominant clonal sequence with ClonoSEQ from pre-treatment specimen or inadequate tissue for testing

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Adaptive Biotechnologies

INDUSTRY

Sponsor Role: collaborator

Fox Chase Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marcus Messmer

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Central Contacts

Abigail O'Keefe

Role: CONTACT

abigail.o'keefe@fccc.edu

215-728-2451

Other Identifiers

24-1014, HM-225

Identifier Type: -

Identifier Source: org_study_id