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

Recruiting now · Phase 2

Conditions studied: Grade 3b Follicular Lymphoma, High Grade B-Cell Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Transformed Non-Hodgkin Lymphoma

In brief

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.

Key facts

Study ID

NCT05890352

Run by

SWOG Cancer Research Network

People needed

227

Starts

2023-09-26

Expected to finish

2029-01-01

Last updated by the study team

2025-10-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have:
• Histologically confirmed relapsed/refractory LBCL as outlined by the World Health Organization (WHO) guidelines
• Follicular lymphoma, grade 3B
• Transformed lymphoma
• High grade B-cell lymphoma with or without MYC, BCL2 and/or BCL6 rearrangements
• Participants must have staging imaging performed within 28 days prior to registration, as follows. Positron emission tomography (PET)-computed tomography (CT) baseline scans are strongly preferred; diagnostic quality magnetic resonance imaging (MRI), contrast-enhanced CT, or contrast-enhanced MRI scans are also acceptable if PET-CT is not feasible at baseline. Note: PET-CT will be required at end of treatment (EOT) and progression for response assessment. All measurable lesions (longest diameter >= 1.5 cm) must be assessed within 28 days prior to registration. Tests to assess non-measurable disease must be performed within 28 days prior to registration. All disease must be documented on the Baseline Tumor Assessment Form.
• Participants must have cell of origin (COO) determination of germinal center (GC)(GCB or non-GC GCB) of LBCL based on Hans immunohistochemistry algorithm (CD10, BCL6, MUM1) as noted on pathology report.
• Participants must have had 1-5 prior systemic treatment regimens including one systemic multiagent regimen for aggressive lymphoma
• Participants who have received prior systemic therapy must have completed their last treatment prior to registration. Participants must have recovered from previous therapy
• Steroid use for the control of non-Hodgkin lymphoma symptoms is allowable, but must be discontinued prior to Cycle 1, Day 1
• Participant must be >= 18 years old
• Participant must have Zubrod Performance Status of 0-3
• Participant must have a complete medical history and physical exam within 28 days prior to registration
• Absolute neutrophil count >= 1.0 x 10\^3/uL (within 28 days prior to registration)
• If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants must have: Absolute neutrophil count (ANC) >= 0.75 x 10\^3/uL
• Platelets >= 75 x 10\^3/uL (within 28 days prior to registration)
• If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants must have: Platelets >= 50 x 10\^3/uL
• Aspartate aminotransferase (AST) =< 3 x institutional upper limit of normal (IULN), alanine aminotransferase (ALT) =< 3 x IULN (within 28 days prior to registration) unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver.
• Participants with lymphomatous involvement of the liver must have AST =< 5 x IULN, ALT =< 5 x IULN
• Total bilirubin =< 1.5 x IULN (within 28 days prior to registration) unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver.
• Participants with lymphomatous involvement of the liver must have total bilirubin =< 5 x IULN
• Participants must have a calculated creatinine clearance >= 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Participants must have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia
• Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at randomization and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration

You may not qualify if…

• Participants must not have active lymphomatous involvement of the central nervous system (CNS) because the treatments used in this study are not effective to sufficiently penetrate the blood brain barrier
• Participants must not have known abnormalities associated with myelodysplastic syndrome (MDS) (e.g., del 5q, chr 7 abn) and myeloproliferative neoplasms (MPN) (e.g., JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing. Testing is not required for eligibility determination
• Participants must not have a known prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute leukemia (T-ALL). Testing is not required for eligibility determination
• Participants must not be a candidate based on investigator assessment to receive autologous stem cell transplant (ASCT) or must have declined ASCT. Participants who had disease progression after stem cell transplant or cellular therapy (such as chimeric antigen receptor (CAR) T-cell) are eligible
• Participants must not have received prior treatment with tafasitamab and/or lenalidomide
• Participants must not have had prior BTK inhibitor or tazemetostat
• Participants must not have any known allergy or reaction to any component of tafasitamab, lenalidomide, tazemetostat or zanubrutinib
• Participants must not be receiving direct vitamin K inhibitors or strong or moderate CYP3A inhibitors or inducers at the date of registration
• Notes: Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference
• Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Participants must not be pregnant or nursing and must follow the guidelines according to the lenalidomide Risk Evaluation and Mitigation Strategies (REMS) program. The effects of tazemetostat, zanubrutinib, lenalidomide and tafasitamab, and the combination of these drugs have not been studied on the developing human fetus are the effects are unknown. Individuals who are of reproductive potential must have agreed to use a highly effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential". In addition to routine contraceptive methods, "acceptable contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen

Where it is running

• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States (enrolling)
• Banner University Medical Center - Tucson — Tucson, Arizona, United States (enrolling)
• City of Hope Comprehensive Cancer Center — Duarte, California, United States (enrolling)
• City of Hope Seacliff — Huntington Beach, California, United States (enrolling)
• City of Hope Antelope Valley — Lancaster, California, United States (enrolling)
• Tower Cancer Research Foundation — Beverly Hills, California, United States (enrolling)
• Cedars Sinai Medical Center — Los Angeles, California, United States (enrolling)
• City of Hope Newport Beach — Newport Beach, California, United States (enrolling)
• City of Hope South Pasadena — South Pasadena, California, United States (enrolling)
• City of Hope South Bay — Torrance, California, United States (enrolling)
• City of Hope Upland — Upland, California, United States (enrolling)
• Holy Cross Hospital — Fort Lauderdale, Florida, United States (enrolling)
• City of Hope at Long Beach Elm — Long Beach, California, United States (enrolling)
• University of Illinois — Chicago, Illinois, United States (enrolling)
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States (enrolling)
• Carle at The Riverfront — Danville, Illinois, United States (enrolling)
• Carle Physician Group-Effingham — Effingham, Illinois, United States (enrolling)
• Carle Physician Group-Mattoon/Charleston — Mattoon, Illinois, United States (enrolling)
• UC Comprehensive Cancer Center at Silver Cross — New Lenox, Illinois, United States (enrolling)
• University of Chicago Medicine-Orland Park — Orland Park, Illinois, United States (enrolling)
• Memorial Hospital East — Shiloh, Illinois, United States (enrolling)
• Carle Cancer Center — Urbana, Illinois, United States (enrolling)
• Northwest Cancer Center - Main Campus — Crown Point, Indiana, United States (enrolling)
• Northwest Oncology LLC — Dyer, Indiana, United States (enrolling)
• Northwest Cancer Center - Hobart — Hobart, Indiana, United States (enrolling)

Full record on ClinicalTrials.gov

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