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

Temple University Health System (TUHS)

Status and phase: Not yet enrolling; Phase 2

Conditions: Indolent Non-hodgkin Lymphoma; Lymphoma

Treatments: Drug: Bendamustine; Drug: Rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06557330

24-1014, HM-225

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Single Arm

Experimental group

Description:

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).

Treatment:

Drug: Rituximab

Drug: Bendamustine