Clinical trial NCT06557330: MRD Guided De-intensification of Bendamustine/Rituximab for Indolent Non-Hodgkin Lymphoma
Official title: HM-225: Measurable Residual Disease (MRD) Guided De-intensification of Bendamustine/Rituximab (BR) for Indolent Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Lymphoma
Indolent Non-hodgkin Lymphoma
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
Collaborators: name: Adaptive Biotechnologies
First posted: 2024-08-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: PFS Evaluation
timeFrame: 2 years
measure: Statistical PFS
timeFrame: 2 years
Secondary outcomes:
measure: Secondary Outcome Measure
timeFrame: 2 years
measure: Measurable Residual Disease Evaluation
timeFrame: 2 years
measure: Adverse Event assessment
timeFrame: 2 years
measure: Overall Survival Assessment
timeFrame: 2 years
measure: Measurable Residual Disease Negativity
timeFrame: 2 years
measure: Rate of 3+ adverse events
timeFrame: 2 years
Other outcomes:
measure: Exploratory Outcome Measures
timeFrame: 2 years
measure: Measurable Residual Disease (MRD)
timeFrame: 2 years
measure: Progression Free Survival (PFS) for Measurable Residual Disease (MRD)
timeFrame: 2 years
measure: Measurable Residual Disease (MRD) to guide indolent lymphoma treatment evaluation
timeFrame: 2 years
measure: Measurable Residual Disease (MRD) failure rate
timeFrame: 2 years
measure: Infection occruance
timeFrame: 2 years
measure: Secondary malignancy occurrence
timeFrame: 2 years
measure: Ntural Killer and T cell reconstitution
timeFrame: 2 years
measure: Quality Life Assessment
timeFrame: 2 years
measure: Baseline Proliferative Rate
timeFrame: 2 years
Locations:
Study officials:
affiliation: Fox Chase Cancer Center
name: Marcus Messmer
role: PRINCIPAL_INVESTIGATOR
References: