Indolent Non-hodgkin Lymphoma, Lymphoma
Conditions
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.
Interventions
DRUGBendamustine
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.
DRUGRituximab
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.
Sponsors
Adaptive Biotechnologies
Fox Chase Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event assessment | 2 years | Assess adverse effects of 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), |
| 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. |
| Measurable Residual Disease Negativity | 2 years | To evaluate MRD negativity rate at the end of treatment and at 2 years post-treatment. |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ntural Killer and T cell reconstitution | 2 years | Assess the rate of NK (natural kiler) cell and T cell subset reconstitution after Bendamustine and Rituximab; distinguish if there is difference between shorter/longer treatment regimens |
| Baseline Proliferative Rate | 2 years | Correlation of baseline proliferative rate |
| Quality Life Assessment | 2 years | Assess differences in quality of life based on Functional Assessment of Cancer Therapy (FACT-Lym) questionnaire between patients who received varying lengths of treatment. |
| Exploratory Outcome Measures | 2 years | Assess and compare measurable residual disease (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 |
| Measurable Residual Disease (MRD) | 2 years | Assess MRD level, both ctDNA and circulating tumor cell (CTC) testing, after each cycle of Bendamustine and Rituximab (BR) and correlate with Progression Free Survival (PFS) |
| Progression Free Survival (PFS) for Measurable Residual Disease (MRD) | 2 years | To evaluate PFS for patients with low level detectable MRD (10\^-4 to 10\^-6) after 3 cycles of Bendamustine and Rituximab |
| Measurable Residual Disease (MRD) to guide indolent lymphoma treatment evaluation | 2 years | Evaluate feasibility of using MRD to guide treatment for indolent lymphoma |
| Measurable Residual Disease (MRD) failure rate | 2 years | Determine MRD test baseline failure rate from ctDNA and Circulating Tumor Cell (CTC) testing |
| Infection occruance | 2 years | Assess occurrence of infection of any grade |
| Secondary malignancy occurrence | 2 years | Assess occurrence of secondary malignancy |
Contacts
Primary ContactAbigail O'Keefe
Outcome results
None listed