Testing Drug Treatments After CAR T-cell Therapy in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

January 30, 2026 updated by: SWOG Cancer Research Network

A Randomized Phase II Trial of Consolidation Therapy Following CD19 CAR T-Cell Treatment for Relapsed/Refractory Diffuse Large B-Cell Lymphoma or Grade IIIB Follicular Lymphoma

This phase II trial tests whether mosunetuzumab and/or polatuzumab vedotin helps benefit patients who have received chemotherapy (fludarabine and cyclophosphamide) followed by chimeric antigen receptor (CAR) T-cell therapy (tisagenlecleucel, axicabtagene ciloleucel, or lisocabtagene maraleucel) for diffuse large B-cell lymphoma that has come back (recurrent) or that does not respond to treatment (refractory) or grade IIIb follicular lymphoma. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Polatuzumab vedotin is a monoclonal antibody, called polatuzumab, linked to a drug called vedotin. Polatuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, and delivers vedotin to kill them. Chemotherapy drugs, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving mosunetuzumab and/or polatuzumab vedotin after chemotherapy and CAR T-cell therapy may be more effective at controlling or shrinking the cancer than not giving them.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the progression-free survival in participants with relapsed/refractory large B-cell lymphoma or follicular lymphoma grade 3B with stable disease (SD) or partial remission (PR) on first imaging response by central review (day +30 positron emission tomography [PET]/computed tomography [CT] scan) after commercial CD19 CAR T-cell therapy who are randomized to receive each consolidation therapy versus those that receive no consolidation therapy (i.e. control).

Ia. Specifically, to compare the progression free survival (PFS) of 1) mosunetuzumab consolidation to no consolidation, 2) polatuzumab vedotin consolidation to no consolidation, 3) mosunetuzumab + polatuzumab vedotin to no consolidation.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) in participants randomized to each consolidation treatment arm versus control.

II. To compare the complete remission (CR) conversion rate up to one year in participants randomized to each consolidation arm versus control.

III. To evaluate the treatment-related adverse events in participants randomized to each consolidation arm.

IV. To evaluate the association between total metabolic tumor volume (TMTV), standardized uptake value (SUV) max, and sum product (SPD) of diameters by PET-CT at first imaging response with complete remission conversion up to one year in participants randomized to each consolidation arm as well as those randomized to control.

V. To evaluate the overall response rate (ORR), CR rate, PFS, and OS of participants randomized to Arm 4 (observation) who have lymphoma progression within 12 months of CAR T-cell infusion and subsequently 'cross-over' to receive treatment with mosunetuzumab + polatuzumab vedotin.

VI. To estimate overall survival for all patients registered to this study. VII. To assess the difference in overall survival between participants who achieved CR at first imaging (day +30) versus those who did not achieve CR at first imaging.

BANKING OBJECTIVES:

I. To bank specimens for future correlative studies. II. To bank PET-CT images for future correlative studies.

OUTLINE:

STEP I: Patients receive lymphodepleting chemotherapy consisting of fludarabine intravenously (IV) and cyclophosphamide IV on study. Patients then receive tisagenlecleucel IV, axicabtagene ciloleucel IV, or lisocabtagene maraleucel IV on study.

STEP II: Patients are randomized to 1 of 4 arms.

ARM I: Patients receive mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

ARM II: Patients receive polatuzumab vedotin IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

ARM III: Patients receive polatuzumab vedotin IV and mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

ARM IV: Patients undergo observation on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study. Patients with subsequent progression within 12 months of CAR T-cell therapy may crossover to Arm III.

Study Type

Interventional

Enrollment (Estimated)

396

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • Banner University Medical Center - Tucson
        • Principal Investigator:
          • Muhammad Husnain
        • Contact:
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • University of Arizona Cancer Center-North Campus
        • Principal Investigator:
          • Muhammad Husnain
        • Contact:
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Recruiting
        • Highlands Oncology Group - Fayetteville
        • Principal Investigator:
          • Joseph T. Beck
        • Contact:
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • University of Arkansas for Medical Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 501-686-8274
        • Principal Investigator:
          • Cesar Gentille
      • Rogers, Arkansas, United States, 72758
        • Recruiting
        • Highlands Oncology Group - Rogers
        • Principal Investigator:
          • Joseph T. Beck
        • Contact:
      • Springdale, Arkansas, United States, 72762
        • Recruiting
        • Highlands Oncology Group
        • Principal Investigator:
          • Joseph T. Beck
        • Contact:
    • California
      • Costa Mesa, California, United States, 92627
        • Recruiting
        • UC Irvine Health Cancer Center-Newport
        • Principal Investigator:
          • Elizabeth A. Brem
        • Contact:
          • Site Public Contact
          • Phone Number: 877-827-8839
      • Irvine, California, United States, 92612
        • Recruiting
        • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
        • Contact:
        • Principal Investigator:
          • Elizabeth A. Brem
      • Laguna Hills, California, United States, 92653
        • Recruiting
        • UCI Health Laguna Hills
        • Contact:
        • Principal Investigator:
          • Elizabeth A. Brem
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Elizabeth A. Brem
      • San Francisco, California, United States, 94143
        • Recruiting
        • UCSF Medical Center-Parnassus
        • Contact:
          • Site Public Contact
          • Phone Number: 877-827-3222
        • Principal Investigator:
          • Madhav R. Seshadri
    • Florida
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • UF Health Cancer Institute - Gainesville
        • Contact:
        • Principal Investigator:
          • Dina G. Khalaf
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital/Winship Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 404-778-1868
        • Principal Investigator:
          • Kristie A. Blum
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Emory Saint Joseph's Hospital
        • Principal Investigator:
          • Kristie A. Blum
        • Contact:
          • Site Public Contact
          • Phone Number: 404-851-7115
    • Idaho
      • Boise, Idaho, United States, 83712
        • Recruiting
        • Saint Luke's Cancer Institute - Boise
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Fruitland, Idaho, United States, 83619
        • Recruiting
        • Saint Luke's Cancer Institute - Fruitland
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Meridian, Idaho, United States, 83642
        • Recruiting
        • Saint Luke's Cancer Institute - Meridian
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Nampa, Idaho, United States, 83687
        • Recruiting
        • Saint Luke's Cancer Institute - Nampa
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Twin Falls, Idaho, United States, 83301
        • Recruiting
        • Saint Luke's Cancer Institute - Twin Falls
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Justin P. Kline
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois
        • Contact:
          • Site Public Contact
          • Phone Number: 312-355-3046
        • Principal Investigator:
          • Carlos Galvez
      • Maywood, Illinois, United States, 60153
        • Suspended
        • Loyola University Medical Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa/Holden Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-237-1225
        • Principal Investigator:
          • Eric Mou
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Cancer Center
        • Principal Investigator:
          • Marc S. Hoffmann
        • Contact:
      • Overland Park, Kansas, United States, 66210
        • Recruiting
        • University of Kansas Cancer Center-Overland Park
        • Principal Investigator:
          • Marc S. Hoffmann
        • Contact:
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Hospital-Westwood Cancer Center
        • Principal Investigator:
          • Marc S. Hoffmann
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • The James Graham Brown Cancer Center at University of Louisville
        • Contact:
          • Site Public Contact
          • Phone Number: 502-562-3429
        • Principal Investigator:
          • Hassaan Yasin
      • Louisville, Kentucky, United States, 40245
        • Recruiting
        • UofL Health Medical Center Northeast
        • Contact:
        • Principal Investigator:
          • Hassaan Yasin
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University/Sidney Kimmel Cancer Center
        • Contact:
        • Principal Investigator:
          • Cole H. Sterling
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland/Greenebaum Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-888-8823
        • Principal Investigator:
          • Jean A. Yared
    • Michigan
      • Battle Creek, Michigan, United States, 49017
        • Recruiting
        • Bronson Battle Creek
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Wayne State University/Karmanos Cancer Institute
        • Principal Investigator:
          • Joseph P. Uberti
        • Contact:
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Contact:
        • Principal Investigator:
          • Philip Kuriakose
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Weisberg Cancer Treatment Center
        • Principal Investigator:
          • Joseph P. Uberti
        • Contact:
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Trinity Health Grand Rapids Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Kalamazoo, Michigan, United States, 49007
        • Recruiting
        • Bronson Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Kalamazoo, Michigan, United States, 49007
        • Recruiting
        • West Michigan Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Kalamazoo, Michigan, United States, 49009
        • Recruiting
        • Beacon Kalamazoo Cancer Center
        • Principal Investigator:
          • Kathleen Y. Butler
        • Contact:
          • Site Public Contact
          • Phone Number: 574-647-7370
      • Muskegon, Michigan, United States, 49444
        • Recruiting
        • Trinity Health Muskegon Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Niles, Michigan, United States, 49120
        • Recruiting
        • Corewell Health Lakeland Hospitals - Niles Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 616-391-1230
        • Principal Investigator:
          • Kathleen Y. Butler
      • Norton Shores, Michigan, United States, 49444
        • Recruiting
        • Cancer and Hematology Centers of Western Michigan - Norton Shores
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Reed City, Michigan, United States, 49677
        • Recruiting
        • Corewell Health Reed City Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Saint Joseph, Michigan, United States, 49085
        • Recruiting
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Southfield, Michigan, United States, 48075
        • Active, not recruiting
        • Henry Ford Health Providence Southfield Hospital
      • Traverse City, Michigan, United States, 49684
        • Recruiting
        • Munson Medical Center
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
      • Wyoming, Michigan, United States, 49519
        • Recruiting
        • University of Michigan Health - West
        • Contact:
        • Principal Investigator:
          • Kathleen Y. Butler
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Recruiting
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
        • Contact:
        • Principal Investigator:
          • Charles Gaulin
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Recruiting
        • University of New Mexico Cancer Center
        • Contact:
        • Principal Investigator:
          • Matthew Fero
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Hua-Jay J. Cherng
      • New York, New York, United States, 10065
        • Suspended
        • NYP/Weill Cornell Medical Center
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 585-275-5830
        • Principal Investigator:
          • Patrick M. Reagan
      • Webster, New York, United States, 14580
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Carolinas Medical Center/Levine Cancer Institute
        • Principal Investigator:
          • Nilanjan Ghosh
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-9376
      • Concord, North Carolina, United States, 28025
        • Recruiting
        • Atrium Health Cabarrus/LCI-Concord
        • Principal Investigator:
          • Nilanjan Ghosh
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-9376
      • Durham, North Carolina, United States, 27710
        • Suspended
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Principal Investigator:
          • Rakhee Vaidya
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
    • North Dakota
      • Fargo, North Dakota, United States, 58122
      • Fargo, North Dakota, United States, 58122
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • Case Western Reserve University
        • Contact:
        • Principal Investigator:
          • Changchun Deng
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Principal Investigator:
          • Sami Ibrahimi
        • Contact:
    • Oregon
      • Newberg, Oregon, United States, 97132
        • Recruiting
        • Providence Newberg Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Oregon City, Oregon, United States, 97045
        • Recruiting
        • Providence Willamette Falls Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
        • Contact:
        • Principal Investigator:
          • Andy I. Chen
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Saint Vincent Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Recruiting
        • Geisinger Medical Center
        • Principal Investigator:
          • Joseph P. Lynch
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania/Abramson Cancer Center
        • Principal Investigator:
          • Nasheed M. Hossain
        • Contact:
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Recruiting
        • Geisinger Wyoming Valley/Henry Cancer Center
        • Principal Investigator:
          • Joseph P. Lynch
        • Contact:
    • South Carolina
      • Boiling Springs, South Carolina, United States, 29316
        • Recruiting
        • Prisma Health Cancer Institute - Spartanburg
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
        • Principal Investigator:
          • Brian T. Hess
      • Easley, South Carolina, United States, 29640
        • Recruiting
        • Prisma Health Cancer Institute - Easley
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health Cancer Institute - Faris
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health Cancer Institute - Butternut
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Greenville, South Carolina, United States, 29615
        • Recruiting
        • Prisma Health Cancer Institute - Eastside
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Greer, South Carolina, United States, 29650
        • Recruiting
        • Prisma Health Cancer Institute - Greer
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Seneca, South Carolina, United States, 29672
        • Recruiting
        • Prisma Health Cancer Institute - Seneca
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • Recruiting
        • Baptist Memorial Hospital and Cancer Center-Memphis
        • Contact:
        • Principal Investigator:
          • Brion V. Randolph
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Recruiting
        • University of Vermont Medical Center
        • Principal Investigator:
          • James N. Gerson
        • Contact:
          • Site Public Contact
          • Phone Number: 802-656-4101
          • Email: rpo@uvm.edu
      • Burlington, Vermont, United States, 05405
        • Recruiting
        • University of Vermont and State Agricultural College
        • Principal Investigator:
          • James N. Gerson
        • Contact:
          • Site Public Contact
          • Phone Number: 802-656-8990
          • Email: rpo@uvm.edu
      • Saint Johnsbury, Vermont, United States, 05819
        • Recruiting
        • Dartmouth Cancer Center - North
        • Contact:
        • Principal Investigator:
          • Charles Gaulin
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • VCU Massey Comprehensive Cancer Center
        • Principal Investigator:
          • Sneha Purvey
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98122
        • Recruiting
        • Swedish Medical Center-First Hill
        • Principal Investigator:
          • Charles W. Drescher
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center - University Hospital
        • Principal Investigator:
          • Priyanka Pophali
        • Contact:
      • Madison, Wisconsin, United States, 53718
        • Recruiting
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
        • Principal Investigator:
          • Priyanka Pophali
        • Contact:
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-3666
        • Principal Investigator:
          • Mehdi Hamadani
      • New Berlin, Wisconsin, United States, 53151
        • Recruiting
        • Froedtert and MCW Moorland Reserve Health Center
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-0505
        • Principal Investigator:
          • Mehdi Hamadani

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • STEP 1: REGISTRATION: Participants must have a histologically confirmed diagnosis of diffuse large B-cell lymphoma or follicular lymphoma grade 3b or primary mediastinal large B-cell lymphoma (PMBCL)
  • STEP 1: REGISTRATION: Participants with transformed DLBCL must have transformed DLBCL from follicular or marginal zone lymphoma
  • STEP 1: REGISTRATION: Participant must have bi-dimensionally measurable systemic disease (at least one lesion with longest diameter > 1.5 cm)
  • STEP 1: REGISTRATION: Participants with secondary central nervous system (CNS) lymphoma (parenchymal, spinal cord, meningeal, cerebrospinal fluid involvement) must be asymptomatic from their CNS disease
  • STEP 1: REGISTRATION: Participants must be registered for step 1 after they have signed institutional consent for CAR T-cell leukapheresis but prior to the start of lymphodepleting (LD) chemotherapy for commercial CAR T-cell product

  • STEP 1: REGISTRATION: In the opinion of the enrolling physician, participants must be felt to be a candidate for CAR T-cell therapy with plans to be treated with Food and Drug Administration (FDA) approved commercially available CD19 CAR T-cell construct.

    • Participants must qualify for commercially approved CD19 CAR T-cell therapy per FDA package insert.
    • If the CAR T-cell product does not meet parameters to be given as an FDA approved product (i.e. does not meet specification criteria mandated by FDA and is infused under an expanded access protocol [EAP] or single participant investigational new drug [IND]) the participant will be taken off of study and no longer be eligible for step 2 randomization

  • STEP 1: REGISTRATION: Participants are permitted to receive or have received 'bridging therapy' after CAR T-cell leukapheresis. However, participants must not receive polatuzumab vedotin, and/or mosunetuzumab as part of bridging therapy.

    • Bridging therapy is defined as lymphoma directed therapy administered between leukapheresis and the start of LD chemotherapy. This includes cytotoxic chemotherapy (e.g.: bendamustine and rituximab [BR], rituximab, gemcitabine and oxaliplatin [R-gem/ox]), radiation, corticosteroids, as well as novel therapies such as BTK inhibitors (e.g.: Ibrutinib), immunomodulators (e.g.: lenalidomide), monoclonal antibodies (e.g.: rituximab, obinutuzumab, tafasitamab) antibody drug conjugates (e.g: loncastuximab), checkpoint inhibitors (e.g.: pembrolizumab, nivolumab), clinical trial treatments, etc.
    • If a participant receives polatuzumab vedotin or mosunetuzumab as bridging they will ineligible to continue on step 1 registration portion of the study and be ineligible for step 2 randomization

  • STEP 1: REGISTRATION: PET-CT scan must be planned for completion within 60 days prior to the start of LD chemotherapy.

    • All pre-CAR T-cell therapy disease must be assessed and documented on the baseline/pre-registration tumor assessment form.
    • If receiving bridging therapy, participants must have a PET-CT scan upon completion of all planned bridging therapy. If the PET-CT scan after completion of bridging therapy is consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization.
    • Participants are permitted to receive corticosteroids after leukapheresis without the need to repeat a PET-CT scan. If steroids are used, they must be planned to stop no later than 3 days before CAR -T cell infusion.
    • If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
  • STEP 1: REGISTRATION: Participants that have previously been treated with polatuzumab vedotin or mosunetuzumab prior to CAR T-cell leukapheresis for either indolent or aggressive NHL are eligible as long as the participant did not have refractory disease or progression/relapse within 6 months of the last infusion with either agent
  • STEP 1: REGISTRATION: Participants must be planning to receive CAR T-cell infusion no earlier than 2 days and no later than 14 days after completion of the last day of lymphodepleting chemotherapy. Any participant receiving CAR T-cell infusion outside of this window will be ineligible for step 2 randomization
  • STEP 1: REGISTRATION: LD chemotherapy prior to CAR T-cell infusion must be planned to start within 60 days after step 1 registration
  • STEP 1: REGISTRATION: Participants must be >= 18 years of age at the time of registration
  • STEP 1: REGISTRATION: Participants must have Zubrod performance score (PS) of 0, 1, or 2

  • STEP 1: REGISTRATION: Total bilirubin =< 2 x institutional upper limit of normal (ULN) (within 14 days prior to registration)

    • Unless due to Gilbert's disease or lymphomatous involvement of liver
  • STEP 1: REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x institutional ULN (within 14 days prior to registration)
  • STEP 1: REGISTRATION: Creatinine clearance >= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 14 days prior to registration. Estimated creatinine clearance is based on actual body weight

  • STEP 1: REGISTRATION: Participants must have an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 60 days prior to registration with a cardiac ejection fraction >= 40%.

    • Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better.
    • Participants must not have documented myocardial infarction and percutaneous coronary intervention (PCI) within 6 months prior to registration or myocardial infarction without PCI within 3 months of registration, or unstable angina
  • STEP 1: REGISTRATION: Participants with peripheral neuropathy must have < grade 2
  • STEP 1: REGISTRATION: Participants with hepatitis B virus infection must have undetectable viral load within 14 days prior to registration, be on suppressive therapy and have no evidence of hepatitis B virus (HBV) related hepatic damage
  • STEP 1: REGISTRATION: Participants with hepatitis C infection must have eradication therapy completed, have no evidence of hepatitis C infection (HCV) related damage and have undetectable viral load within 14 days prior to registration
  • STEP 1: REGISTRATION: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration

  • STEP 1: REGISTRATION: Participants must be offered the opportunity to participate in banking for planned translational medicine and future research. With participant consent, any residuals from the mandatory tissue submission will also be banked for future research.

    • Note: Streck tubes must be ordered in advance. Please allow 5-7 days for shipment of the collection kits

  • STEP 1: REGISTRATION: NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

    • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.

      • For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
  • STEP 2: RANDOMIZATION: Participants must have met all eligibility criteria for step 1 registration
  • STEP 2: RANDOMIZATION: Participant's CAR T-cell product must have met specification parameters to be given as an FDA approved commercial product

  • STEP 2: RANDOMIZATION: Participants must have a PET-CT scan between days 25-40 after CAR T-cell infusion and determined to have a response consistent with stable disease or partial remission by central review compared to most recent pre-LD chemo/CAR T-cell PET-CT scan.

    • Note: Patients with delayed enrollment > 21 days after 'day +30' PET-CT scan will necessitate a repeat PET-CT scan if concerning signs or symptoms of lymphoma progression develop.
    • Note: If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
  • STEP 2: RANDOMIZATION: Eligible participants must be randomized no later than 60 days after CAR -T infusion
  • STEP 2: RANDOMIZATION: Participants must have started LD chemotherapy within 60 days of signing consent for step 1 registration
  • STEP 2: RANDOMIZATION: Participants must have S2114 CAR T-cell therapy form submitted to Southwest Oncology Group (SWOG) prior to step 2 randomization

  • STEP 2: RANDOMIZATION: Participants must have had a PET-CT scan upon completion of all planned bridging therapy if received, with the exception of up to 7 days of corticosteroids. If the PET-CT scan after completion of bridging therapy was consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization.

    • If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
  • STEP 2: RANDOMIZATION: Participants must have Zubrod PS of 0, 1, or 2
  • STEP 2: RANDOMIZATION: Absolute neutrophil count (ANC) >= 1.0 x 10^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization)
  • STEP 2: RANDOMIZATION: Platelets >= 75 x 10^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization)

  • STEP 2: RANDOMIZATION: Total bilirubin =< 2 x institutional ULN (within 7 days prior to step 2 randomization)

    • Unless due to Gilbert's disease or lymphomatous involvement of liver
  • STEP 2: RANDOMIZATION: AST and ALT =< 3 x institutional ULN (within 7 days prior to step 2 randomization)
  • STEP 2: RANDOMIZATION: Creatinine clearance >= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 7 days prior to step 2 randomization. Estimated creatinine clearance is based on actual body weight (within 7 days prior to step 2 randomization)
  • STEP 2: RANDOMIZATION: Participants with peripheral neuropathy must have < grade 2
  • STEP 2: RANDOMIZATION: Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
  • STEP 2: RANDOMIZATION: Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 2 randomization and on suppressive therapy
  • STEP 2: RANDOMIZATION: Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 2 randomization
  • STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be continuing to receive anti-retroviral therapy and have an undetectable viral load test within 14 days prior to step 2 randomization
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have documented disease progression while on Arm 4 (observation) on this protocol. The follow-up tumor assessment form documenting disease progression must be submitted to SWOG prior to step 3 crossover registration
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must be registered within 28 days of the date of progression

  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have imaging that clearly demonstrates progression compared to day +30 PET-CT scan

    • Note: These scans should be performed as standard of care and only performed between scheduled response assessments required for study if symptoms arise that are concerning for progression
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have Zubrod PS of 0, 1, or 2
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): ANC >= 1.0 x 10^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration)
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Platelets >= 75 x 10^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration)

  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Total bilirubin =< 2 x institutional ULN (within 14 days prior to step 3 crossover registration)

    • Unless due to Gilbert's disease or lymphomatous involvement of liver
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): AST and ALT =< 3 x institutional ULN
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Creatinine clearance >= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within days prior to step 3 crossover registration. Estimated creatinine clearance is based on actual body weight (within 14 days prior to step 3 crossover registration)
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with peripheral neuropathy must have < grade 2
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration and on suppressive therapy
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration
  • STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with known human immunodefici

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Step I (lymphodepleting chemotherapy)
Patients receive lymphodepleting chemotherapy consisting of fludarabine IV and cyclophosphamide IV on study. Patients then receive tisagenlecleucel IV, axicabtagene ciloleucel IV, or lisocabtagene maraleucel IV on study.
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Fludarabine
Given IV
Other Names:
  • Fluradosa
Biological: Axicabtagene Ciloleucel
Given IV
Other Names:
  • Yescarta
  • KTE C19
  • KTE-C19
  • KTE-C19 CAR
Procedure: Positron Emission Tomography
Undergo PET-CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
Biological: Lisocabtagene Maraleucel
Given IV
Other Names:
  • JCAR017
  • Breyanzi
  • Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes JCAR017
  • Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes JCAR017
  • Autologous Anti-CD19-EGFRt-4-1BB-zeta-modified CAR CD8+ and CD4+ T-lymphocytes JCAR017
  • JCAR 017
Biological: Tisagenlecleucel
Given IV
Other Names:
  • CART19
  • CTL019
  • Kymriah
  • CART-19
  • CTL019 T-cells
  • Tisagenlecleucel-T
Experimental: Step II Arm I (mosunetuzumab)
Patients receive mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.
Procedure: Biospecimen Collection
Undergo collection of blood and tissue samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Computed Tomography
Undergo PET-CT or CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
Procedure: Positron Emission Tomography
Undergo PET-CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
Biological: Mosunetuzumab
Given IV
Other Names:
  • RO7030816
  • BTCT4465A
  • Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A
  • BTCT 4465A
  • BTCT-4465A
  • CD20/CD3 BiMAb BTCT4465A
  • RG 7828
  • RG-7828
  • RG7828
Experimental: Step II Arm II (polatuzumab vedotin)
Patients receive polatuzumab vedotin IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.
Procedure: Biospecimen Collection
Undergo collection of blood and tissue samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Computed Tomography
Undergo PET-CT or CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
Procedure: Positron Emission Tomography
Undergo PET-CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
Drug: Polatuzumab Vedotin
Given IV
Other Names:
  • DCDS4501A
  • ADC DCDS4501A
  • Antibody-Drug Conjugate DCDS4501A
  • FCU 2711
  • polatuzumab vedotin-piiq
  • Polivy
  • RG7596
  • Ro 5541077-000
Experimental: Step II Arm III (polatuzumab vedotin, mosunetuzumab)
Patients receive polatuzumab vedotin IV and mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.
Procedure: Biospecimen Collection
Undergo collection of blood and tissue samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Computed Tomography
Undergo PET-CT or CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
Procedure: Positron Emission Tomography
Undergo PET-CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
Drug: Polatuzumab Vedotin
Given IV
Other Names:
  • DCDS4501A
  • ADC DCDS4501A
  • Antibody-Drug Conjugate DCDS4501A
  • FCU 2711
  • polatuzumab vedotin-piiq
  • Polivy
  • RG7596
  • Ro 5541077-000
Biological: Mosunetuzumab
Given IV
Other Names:
  • RO7030816
  • BTCT4465A
  • Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A
  • BTCT 4465A
  • BTCT-4465A
  • CD20/CD3 BiMAb BTCT4465A
  • RG 7828
  • RG-7828
  • RG7828
Active Comparator: Step II Arm IV (observation)
Patients undergo observation on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study. Patients with subsequent progression within 12 months of CAR T-cell therapy may crossover to Arm III.
Other: Patient Observation
Undergo observation
Other Names:
  • Observation
  • Active Surveillance
  • deferred therapy
  • expectant management
  • Watchful Waiting
Procedure: Biospecimen Collection
Undergo collection of blood and tissue samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Computed Tomography
Undergo PET-CT or CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
Procedure: Positron Emission Tomography
Undergo PET-CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: From date of randomization to date of first observation of progressive disease or death due to any cause, assessed up to 2 years
Will compare PFS in participants with relapsed/refractory large B-cell lymphoma or follicular lymphoma grade 3B with stable disease (SD) or partial remission (PR) on first imaging response (day +30 positron emission tomography [PET]/computed tomography [CT] scan) after commercial CD19 chimeric antigen receptor (CAR) T-cell therapy who are randomized to receive each consolidation therapy versus those that receive no consolidation therapy (i.e. control). Specifically, will compare the PFS of 1) mosunetuzumab consolidation to no consolidation, 2) polatuzumab vedotin consolidation to no consolidation, 3) mosunetuzumab + polatuzumab vedotin to no consolidation. Will analyze results by arm rather than assuming no-interactions in some factorial analyses. Will follow multi-step hypothesis testing procedure of Freidlin and Korn to compare the arms within this randomized Phase II study. Each of the primary comparisons has 81% power using a stratified logrank test at one-sided alpha of 0.05.
From date of randomization to date of first observation of progressive disease or death due to any cause, assessed up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: Up to 2 years
Up to 2 years
Overall survival (OS)
Time Frame: From date of randomization to date of death due to any cause, assessed up to 2 years
Will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.
From date of randomization to date of death due to any cause, assessed up to 2 years
Complete remission (CR) conversion rate
Time Frame: Up to 1 year after randomization
The complete remission conversion rate up to one year after randomization will be calculated and compared using Cochran-Mantel-Haenszel test with a two-sided alpha of .05.
Up to 1 year after randomization
Association between total metabolic tumor volume (TMTV), standardized uptake value (SUV) max, and sum product (SPD) of diameters
Time Frame: Up to 2 years
The association between TMTV, SUV max, and SPD by PET-CT at first imaging response as a continuous variable will be assessed using a univariate logistic regression with a two-sided alpha of .05, respectively.
Up to 2 years
Conversion of CR
Time Frame: Up to 2 years
Evaluated as a binary variable. Assessed using a univariate logistic regression with a two-sided alpha of 0.05.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SWOG Cancer Research Network

Collaborators

National Cancer Institute (NCI)
Genentech, Inc.

Investigators

  • Principal Investigator: Brian T Hess, SWOG Cancer Research Network

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 12, 2023

Primary Completion (Estimated)

June 30, 2030

Study Completion (Estimated)

June 30, 2030

Study Registration Dates

First Submitted

November 21, 2022

First Submitted That Met QC Criteria

November 21, 2022

First Posted (Actual)

December 1, 2022

Study Record Updates

Last Update Posted (Actual)

February 2, 2026

Last Update Submitted That Met QC Criteria

January 30, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S2114 (Other Identifier: CTEP)
  • U10CA180888 (U.S. NIH Grant/Contract)
  • NCI-2022-07930 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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