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

NCT06557330 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-1014, HM-225
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Lymphoma; Indolent Non-hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• PFS Evaluation

  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.

  2 years

• Statistical PFS

  The proportion (p) of patients who are progression-free and are alive at 2 years from the initiation of treatment using Lugano Criteria.

  2 years

Secondary Outcomes (6)

• Secondary Outcome Measure

  2 years

• Measurable Residual Disease Evaluation

  2 years

• Adverse Event assessment

  2 years

• Overall Survival Assessment

  2 years

• Measurable Residual Disease Negativity

  2 years

Other Outcomes (10)

• Exploratory Outcome Measures

  2 years

• Measurable Residual Disease (MRD)

  2 years

• Progression Free Survival (PFS) for Measurable Residual Disease (MRD)

  2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

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).

Drug: Bendamustine; Drug: Rituximab

Interventions

Bendamustine 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.

Also known as: cytostasan, belrapzo, treanda, vivimusta

Single Arm

Rituximab 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.

Also known as: riabni, Rituxan, Ruxience, Truxima, Azulfidine

Single Arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• Adaptive Biotechnologies: collaborator

MeSH Terms

Conditions

Lymphoma

Interventions

Bendamustine Hydrochloride; Rituximab; Sulfasalazine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfonamides; Amides; Sulfones; Sulfur Compounds

Study Officials

• Marcus Messmer

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abigail O'Keefe

CONTACT

215-728-2451; abigail.o'keefe@fccc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2024
• First Posted: August 16, 2024
• Study Start: June 1, 2025
• Primary Completion (Estimated): September 29, 2027
• Study Completion (Estimated): March 30, 2028
• Last Updated: January 6, 2025

Record last verified: 2025-01