This phase II trial studies how well measurable residual disease (MRD) detection works as a tool to reduce the amount (de-intensification) of bendamustine and rituximab in treating patients with non-Hodgkin lymphoma that tends to grow and spread slowly, and has few symptoms (indolent). Patients with indolent non-Hodgkin lymphoma are given at least 6 cycles of treatment therapy as standard-of-care. However, some patients have a good response to treatment after a few cycles (less than 6 cycles). It might be helpful for these patients to reduce the number of treatment cycles and begin the observation period sooner and safely wait to start the next round of therapy. This trial uses new laboratory tests that can measure small amounts of circulating tumor cells (called CTCs) and circulating tumor deoxyribonucleic acid (DNA) that are released from the tumor into the blood, called MRD. Changes in MRD levels have been found to be related to whether tumors are getting bigger or smaller. Chemotherapy drugs, such as bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. MRD-guided de-intensification of bendamustine and rituximab may be able to reduce potential long-term harmful side effects of the repeated treatment for indolent non-Hodgkin lymphoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06557330.
Locations matching your search criteria
United States
Pennsylvania
Philadelphia
Fox Chase Cancer CenterStatus: Temporarily closed to accrual
Contact: Marcus Messmer
Phone: 215-728-2978
PRIMARY OBJECTIVE:
I. To evaluate the 2-year progression free survival (PFS) for patients treated with bendamustine/rituximab (BR) with MRD directed duration of therapy.
SECONDARY OBJECTIVES:
I. To assess additional clinical outcomes including overall survival (OS).
II. To determine the rate of MRD negativity at end of treatment and at 2 years post-treatment.
III. Assess adverse effects of treatment.
EXPLORATORY OBJECTIVES:
I. Assess and compare MRD sensitivity of both circulating tumor DNA (ctDNA) and circulating tumor cells (CTC), both being obtained at baseline, after each cycle, and during follow up.
II. Assess MRD level, both ctDNA and CTC testing, after each cycle of BR and correlate with PFS.
III. To evaluate PFS for patients with low level detectable MRD (10^-4 to 10^-6) after 3 cycles of BR.
IV. Evaluate feasibility of using MRD to guide treatment for indolent lymphoma.
V. Determine MRD test baseline failure rate from ctDNA and CTC testing.
VI. Assess occurrence of infection of any grade.
VII. Assess occurrence of secondary malignancy.
VIII. Assess the rate of natural killer (NK) cell and T cell subset reconstitution after BR; distinguish if there is difference between shorter/longer treatment regimens.
IX. Assess differences in quality of life based on Functional Assessment of Cancer Therapy (FACT–Lym) questionnaire between patients who received varying lengths of treatment.
X. Correlation of baseline proliferative rate and cell-in-cell events with 2 year PFS.
OUTLINE:
Patients receive bendamustine intravenously (IV) over 10 minutes on days 1-2 of each cycle and rituximab IV on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD) or progressive disease (PD) after cycle 3 discontinue treatment and proceed to follow-up. Patients with complete response (CR) or partial response (PR) after cycle 3 proceed with cycle 4. After cycle 4, patients with CR and MRD negative discontinue treatment and proceed to follow-up. After cycle 4, patients partial response (PR) with or without MRD OR CR and MRD positive then receive bendamustine IV over 10 minutes on days 1-2 of each cycle and rituximab IV on day 1 of each cycle. Cycles repeat every 28 days for 2 additional cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (CT) or CT and blood sample collection throughout the study. In addition, patients may undergo biopsy as clinically indicated.
After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 2 years, and then every 6 months during year 3-5.
Lead OrganizationFox Chase Cancer Center
Principal InvestigatorMarcus Messmer
