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
3 other identifiers
interventional
227
1 country
104
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2023
Longer than P75 for phase_2
104 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 25, 2023
CompletedFirst Posted
Study publicly available on registry
June 6, 2023
CompletedStudy Start
First participant enrolled
September 26, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2029
October 20, 2025
October 1, 2025
3.3 years
May 25, 2023
October 16, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Progression-free survival (PFS)
Will be compared between participants randomized to control Arm 2 (tafasitamab + lenalidomide) versus (vs) experimental Arm 1 (tafasitamab + lenalidomide + tazemetostat), AND control Arm 2 vs experimental Arm 3 (tafasitamab + lenalidomide + zanubrutinib), respectively.
From date of randomization to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed up to 3 years
Trial Outcome Index (TOI) score from the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) (Patient Reported Outcome [PRO] Study)
Will compare the trial outcome index (TOI) score between each experimental arm (Arm 1 and Arm 3) to the control arm (Arm 2). The TOI score is composed of the Physical Well-Being, Functional Well-Being, and lymphoma-specific subscale scores. The scores range from 0-116, with higher scores indicating a higher quality of life.
Baseline up to 3 months after randomization
Secondary Outcomes (10)
Hazard ratio for PFS in the germinal center B-cell (GCB) subgroup
Up to 3 years
Hazard ratio for PFS in the non-GCB subgroup
Up to 3 years
PFS
From date of randomization to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause, assessed up to 3 years
Overall response rate (ORR)
Up to 3 years
Complete response (CR) rate
Up to 3 years
- +5 more secondary outcomes
Study Arms (5)
Part I, Arm I (tafasitamab, lenalidomide, tazemetostat)
EXPERIMENTALPatients 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.
Part I, Arm III (tafasitamab, lenalidomide, zanubrutinib)
EXPERIMENTALPatients 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, Arm I (tafasitamab, lenalidomide, tazemetostat)
EXPERIMENTALPatients 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.
Part II, Arm II (tafasitamab, lenalidomide)
ACTIVE COMPARATORPatients 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.
Part II, Arm III (tafasitamab, lenalidomide, zanubrutinib)
EXPERIMENTALPatients 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.
Interventions
Undergo optional collection of blood
Undergo PET/CT and CT
Given PO
Undergo MRI
Undergo PET/CT
Ancillary studies
Ancillary studies
Given IV
Given PO
Given PO
Eligibility Criteria
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
- +17 more criteria
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- SWOG Cancer Research Networklead
- National Cancer Institute (NCI)collaborator
- BeiGenecollaborator
- Ipsencollaborator
- Incyte Corporationcollaborator
Study Sites (104)
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719, United States
Tower Cancer Research Foundation
Beverly Hills, California, 90211, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
City of Hope Seacliff
Huntington Beach, California, 92648, United States
City of Hope Antelope Valley
Lancaster, California, 93534, United States
City of Hope at Long Beach Elm
Long Beach, California, 90813, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
City of Hope Newport Beach
Newport Beach, California, 92660, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
City of Hope South Bay
Torrance, California, 90503, United States
City of Hope Upland
Upland, California, 91786, United States
Holy Cross Hospital
Fort Lauderdale, Florida, 33308, United States
Mount Sinai Medical Center
Miami Beach, Florida, 33140, United States
University of Illinois
Chicago, Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Northwest Cancer Center - Main Campus
Crown Point, Indiana, 46307, United States
Northwest Oncology LLC
Dyer, Indiana, 46311, United States
Northwest Cancer Center - Hobart
Hobart, Indiana, 46342, United States
Saint Mary Medical Center
Hobart, Indiana, 46342, United States
Saint Catherine Hospital
Indianapolis, Indiana, 46312, United States
The Community Hospital
Munster, Indiana, 46321, United States
Women's Diagnostic Center - Munster
Munster, Indiana, 46321, United States
Northwest Cancer Center - Valparaiso
Valparaiso, Indiana, 46383, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
Mercy Hospital
Cedar Rapids, Iowa, 52403, United States
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114, United States
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188, United States
Trinity Health Medical Center - Canton
Canton, Michigan, 48188, United States
Chelsea Hospital
Chelsea, Michigan, 48118, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118, United States
Cancer Hematology Centers - Flint
Flint, Michigan, 48503, United States
Genesee Hematology Oncology PC
Flint, Michigan, 48503, United States
Genesys Hurley Cancer Institute
Flint, Michigan, 48503, United States
Hurley Medical Center
Flint, Michigan, 48503, United States
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341, United States
Huron Gastroenterology PC
Ypsilanti, Michigan, 48106, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746, United States
Essentia Health Sandstone
Sandstone, Minnesota, 55072, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
University of Rochester
Rochester, New York, 14642, United States
Wilmot Cancer Institute at Webster
Webster, New York, 14580, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Providence Newberg Medical Center
Newberg, Oregon, 97132, United States
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Ben Taub General Hospital
Houston, Texas, 77030, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911, United States
Duluth Clinic Ashland
Ashland, Wisconsin, 54806, United States
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, 53105, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Aurora Health Care Germantown Health Center
Germantown, Wisconsin, 53022, United States
Aurora Cancer Care-Grafton
Grafton, Wisconsin, 53024, United States
Aurora BayCare Medical Center
Green Bay, Wisconsin, 54311, United States
Aurora Cancer Care-Kenosha South
Kenosha, Wisconsin, 53142, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
Aurora Bay Area Medical Group-Marinette
Marinette, Wisconsin, 54143, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Aurora Cancer Care-Milwaukee
Milwaukee, Wisconsin, 53209, United States
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, 53215, United States
Aurora Sinai Medical Center
Milwaukee, Wisconsin, 53233, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548, United States
Vince Lombardi Cancer Clinic - Oshkosh
Oshkosh, Wisconsin, 54904, United States
Aurora Cancer Care-Racine
Racine, Wisconsin, 53406, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Vince Lombardi Cancer Clinic-Sheboygan
Sheboygan, Wisconsin, 53081, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Aurora Medical Center in Summit
Summit, Wisconsin, 53066, United States
Vince Lombardi Cancer Clinic-Two Rivers
Two Rivers, Wisconsin, 54241, United States
Aurora Cancer Care-Milwaukee West
Wauwatosa, Wisconsin, 53226, United States
Aurora West Allis Medical Center
West Allis, Wisconsin, 53227, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jennifer E Amengual
SWOG Cancer Research Network
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 25, 2023
First Posted
June 6, 2023
Study Start
September 26, 2023
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
January 1, 2029
Last Updated
October 20, 2025
Record last verified: 2025-10