Trials / Recruiting

RecruitingNCT05890352

Study Adding Drugs to Usual Treatment for Large B-Cell Lymphoma That Returned or Did Not Respond to Treatment

Randomized Phase II Study of the Addition of Targeted Therapeutic Agents to Tafasitamab-Based Therapy in Non-Transplant-Eligible Patients With Relapsed/Refractory Large B-Cell Lymphoma

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 227 (estimated)

Sponsor: SWOG Cancer Research Network · Network
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase 2 trial studies the side effects and best dose of tazemetostat and zanubrutinib in combination with tafasitamab and lenalidomide, and to see how well these combinations work in treating patients with large B-cell lymphoma that returned or did not respond to earlier treatment. Tazemetostat is in a class of medications called EZH2 inhibitors. It helps to stop the spread of cancer cells. Zanubrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. The addition of tazemetostat or zanubrutinib to tafasitamab and lenalidomide may be able to shrink the cancer or extend the time without cancer symptoms coming back.

Detailed description

PRIMARY OBJECTIVES: I. To determine the recommended phase II dose of tafasitamab + lenalidomide + tazemetostat AND of tafasitamab + lenalidomide + zanubrutinib. (Safety Run-in) II. To compare progression-free survival (PFS) of patients with relapsed/refractory large B-cell lymphoma (R/R LBCL) treated with tafasitamab + lenalidomide + tazemetostat vs control (tafasitamab + lenalidomide) AND treated with tafasitamab + lenalidomide + zanubrutinib versus (vs) control. (Randomized Phase II Study) SECONDARY OBJECTIVES: I. To estimate the hazard ratio for PFS for control vs. tafasitamab + lenalidomide + tazemetostat in germinal center B-cell (GCB) and non-GCB (activated B-cell \[ABC\]/unclassified) subsets. II. To estimate the hazard ratio for PFS for control vs. tafasitamab + lenalidomide + zanubrutinib in GCB and non-GCB (ABC/unclassified) subsets. III. To estimate progression-free survival (PFS), overall response rate (ORR), complete response rate (CR), partial response rate (PR), duration of response (DOR), event-free survival (EFS), overall survival (OS), in GCB and non-GCB LBCL for each treatment. IV. To evaluate adverse events within each treatment arm. OTHER OBJECTIVES: I. To explore PFS within subgroups defined by molecular profile (e.g., MCD, BN2, N1 and EZB) and genetic subtypes. II. To explore PFS in the tafasitamab-lenalidomide control arm vs that in matched historical control from L-MIND and realMIND studies. III. To assess frailty (Cumulative Illness Rating Scale \[CIRS\] and Timed Get Up and Go \[TUG\]) and its correlation with outcome. PRIMARY PATIENT-REPORTED OUTCOMES OBJECTIVE: I. To compare patient-reported lymphoma-specific symptoms as measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Trial Outcome Index sub-scale at 3 months after randomization between the control arm and each experimental arm (Arm 1 versus Arm 2 and Arm 3 versus Arm 2). SECONDARY PATIENT-REPORTED OUTCOMES OBJECTIVE: I. To compare participant-reported toxicity (treatment side effect) symptoms using selected Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) items between experimental vs control arms. EXPLORATORY PATIENT-REPORTED OUTCOMES OBJECTIVES: I. To compare patient-reported quality of life using the FACT-General (G) subscale score and the FACT-Lym total score at 3 months after randomization between the control arm and each experimental arm. II. To compare quality of life over time between treatment arms from baseline to 12 months after randomization as measured by the FACT-Lym trial outcome index (TOI), FACT-G, and FACT-Lym total score using longitudinal analysis. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: This is a dose-escalation study of tazemetostat and zanubrutinib. PART I (SAFETY RUN-IN): Patients are assigned to 1 of 2 arms per treating investigator's choice. ARM I: Patients receive tafasitamab intravenously (IV), lenalidomide orally (PO), and tazemetostat PO on study. Patients also undergo positron emission tomography/computed tomography (PET/CT) and CT or magnetic resonance imaging (MRI) scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study. ARM III: Patients receive tafasitamab IV, lenalidomide PO, and zanubrutinib PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study. PART II: Patients are randomized to 1 of 3 arms. ARM I: Patients receive tafasitamab IV, lenalidomide PO, and tazemetostat PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study. ARM II: Patients receive tafasitamab IV and lenalidomide PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study. ARM III: Patients receive tafasitamab IV, lenalidomide PO, and zanubrutinib PO on study. Patients also undergo PET/CT and CT or MRI scans throughout the trial. Patients also have the option to undergo collection of blood samples during screening and on study.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo optional collection of blood
PROCEDURE	Computed Tomography	Undergo PET/CT and CT
DRUG	Lenalidomide	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
BIOLOGICAL	Tafasitamab	Given IV
DRUG	Tazemetostat	Given PO
DRUG	Zanubrutinib	Given PO

Timeline

Start date: 2023-09-26
Primary completion: 2026-12-31
Completion: 2029-01-01
First posted: 2023-06-06
Last updated: 2025-10-20

Locations

104 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05890352. Inclusion in this directory is not an endorsement.