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

Phase 2

Not yet recruiting

• Conditions: Indolent Non-hodgkin Lymphoma; Lymphoma
• Interventions: Drug: Bendamustine; Drug: Rituximab

• Registration Number: NCT06557330
• Lead Sponsor: Fox Chase Cancer Center

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.

Study Timeline

• Study First Submitted: 2024-08-09
• Study First Submitted QC: 2024-08-13
• Study First Posted: 2024-08-16
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-03
• Last Update Posted: 2025-01-06
• Study Start: 2025-06
• Primary Completion: 2027-09-29
• Study Completion: 2028-03-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	Bendamustine	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).
Single Arm	Rituximab	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).

Primary Outcome Measures

Name	Time	Method
PFS Evaluation	2 years	To evaluate the 2-year progression free survival (PFS) for patients treated with Bendamustine and Rituximab (BR) with measurable residual disease directed (MRD) duration of therapy.
Statistical PFS	2 years	The proportion (p) of patients who are progression-free and are alive at 2 years from the initiation of treatment using Lugano Criteria.

Secondary Outcome Measures

Name	Time	Method
Measurable Residual Disease Negativity	2 years	To evaluate MRD negativity rate at the end of treatment and at 2 years post-treatment.
Overall Survival Assessment	2 years	OS, defined as time from initiation of study treatment until death, or the end of follow-up, whichever occurs first. Patients who are still alive at the end of follow-up will be considered censored.
Secondary Outcome Measure	2 years	Assess additional clinical outcomes including overall survival (OS),
Measurable Residual Disease Evaluation	2 years	To determine the rate of MRD (minimal residual disease) negativity at end of treatment and at 2 years post-treatment
Adverse Event assessment	2 years	Assess adverse effects of treatment
Rate of 3+ adverse events	2 years	The rate of grade 3+ adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.The rate of grade 3+ adverse events as assessed by CTCAE v5.0.