Diffuse Large B-Cell LymphomaPhase 2NCT05633615
Testing Drug Treatments After CAR T-cell Therapy in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
A Phase 2 study testing Axicabtagene Ciloleucel, Biospecimen Collection and Computed Tomography in people with Diffuse Large B-Cell Lymphoma and Grade 3b Follicular Lymphoma, run by SWOG Cancer Research Network at 95 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma, Grade 3b Follicular Lymphoma, Primary Mediastinal (Thymic) Large B-Cell Lymphoma
- What is being tested?
- Axicabtagene Ciloleucel, Biospecimen Collection and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 396 participants
- Where
- 95 sitesUnited States
- Study dates
- 12 Jun 2023to 30 Jun 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
None listed.
Trial locations and contacts
95 sites in 1 country. Contact the study team or a site near you to ask about taking part.
95 sites in 1 country
United States95 sites, 89 recruiting
- Suspended
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
- Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Site Public Contact, 404-778-1868
Kristie A. Blum
- Recruiting
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
Site Public Contact, 404-851-7115
Kristie A. Blum
- Recruiting
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Site Public Contact, 800-888-8823
Jean A. Yared
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Site Public Contact, 410-955-8804, jhcccro@jhmi.edu
Cole H. Sterling
- Recruiting
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana, 70805
Site Public Contact, 225-765-7659, research@ololrmc.com
Nakhle S. Saba
- Recruiting
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana, 70808
Site Public Contact, 225-765-7659, research@ololrmc.com
Nakhle S. Saba
- Recruiting
Bronson Battle Creek
Battle Creek, Michigan, 49017
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Suzanne R. Fanning
- Recruiting
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Site Public Contact, 208-381-2774, eslinget@slhs.org
Charles W. Drescher
- Recruiting
University of Vermont Medical Center
Burlington, Vermont, 05401
Site Public Contact, 802-656-4101, rpo@uvm.edu
James N. Gerson
- Recruiting
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
Site Public Contact, 802-656-8990, rpo@uvm.edu
James N. Gerson
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Site Public Contact, 843-792-9321, hcc-clinical-trials@musc.edu
Brian T. Hess
- Recruiting
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Site Public Contact, 800-804-9376
Nilanjan Ghosh
- Recruiting
University of Illinois
Chicago, Illinois, 60612
Site Public Contact, 312-355-3046
Carlos Galvez
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Justin P. Kline
- Recruiting
Case Western Reserve University
Cleveland, Ohio, 44106
Site Public Contact, 800-641-2422, CTUReferral@UHhospitals.org
Changchun Deng
- Recruiting
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Philip Kuriakose
- Recruiting
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025
Site Public Contact, 800-804-9376
Nilanjan Ghosh
- Recruiting
UC Irvine Health Cancer Center-Newport
Costa Mesa, California, 92627
Site Public Contact, 877-827-8839
Erin Dean
- Recruiting
Geisinger Medical Center
Danville, Pennsylvania, 17822
Site Public Contact, 570-271-5251, cancerresearch@geisinger.edu
Joseph P. Lynch
- Recruiting
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Philip Kuriakose
- Recruiting
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Site Public Contact, 800-527-6266, ctoadmin@karmanos.org
Joseph P. Uberti
- Recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Philip Kuriakose
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Site Public Contact, 888-275-3853
Matthew S. McKinney
- Recruiting
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Suzanne R. Fanning
- Recruiting
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Site Public Contact, 701-323-5760, OncologyClinicalTrialsFargo@sanfordhealth.org
Daniel Almquist
- Recruiting
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Site Public Contact, 701-234-6161, OncologyClinicalTrialsFargo@sanfordhealth.org
Daniel Almquist
- Recruiting
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
Site Public Contact, 313-576-9790, ctoadmin@karmanos.org
Joseph P. Uberti
- Recruiting
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, 72703
Site Public Contact, 479-872-8100, research@hogonc.com
Joseph T. Beck
- Recruiting
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Site Public Contact, 208-381-2774, eslinget@slhs.org
Charles W. Drescher
- Recruiting
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Site Public Contact, 352-273-8010
Muhammad Junaid Tariq
- Recruiting
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Suspended
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
- Recruiting
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Suzanne R. Fanning
- Recruiting
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Suzanne R. Fanning
- Recruiting
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Suzanne R. Fanning
- Recruiting
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Suzanne R. Fanning
- Recruiting
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Site Public Contact, 800-237-1225
Eric Mou
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Erin Dean
- Recruiting
Allegiance Health
Jackson, Michigan, 49201
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Philip Kuriakose
- Recruiting
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Suspended
Beacon Kalamazoo Cancer Center
Kalamazoo, Michigan, 49009
- Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Marc S. Hoffmann
- Recruiting
UCI Health Laguna Hills
Laguna Hills, California, 92653
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Erin Dean
- Recruiting
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
Site Public Contact, 800-639-6918, cancer.research.nurse@dartmouth.edu
Charles Gaulin
- Recruiting
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Site Public Contact, 501-686-8274
Cesar Gentille
- Recruiting
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202
Site Public Contact, 502-562-3429
Hassaan Yasin
- Recruiting
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245
Site Public Contact, 502-852-2755, ctoinfo@louisville.edu
Hassaan Yasin
- Recruiting
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Priyanka Pophali
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Priyanka Pophali
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
Site Public Contact, 708-226-4357
Imran Puthawala
- Recruiting
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Brion V. Randolph
- Recruiting
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Site Public Contact, 208-381-2774, eslinget@slhs.org
Charles W. Drescher
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Site Public Contact, 414-805-3666
Mehdi Hamadani
- Suspended
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444
- Recruiting
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Site Public Contact, 208-381-2774, eslinget@slhs.org
Charles W. Drescher
- Recruiting
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin, 53151
Site Public Contact, 414-805-0505
Mehdi Hamadani
- Recruiting
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Hua-Jay J. Cherng
- Recruiting
NYP/Weill Cornell Medical Center
New York, New York, 10065
Site Public Contact, 212-746-1848
Gaurav Varma
- Recruiting
Providence Newberg Medical Center
Newberg, Oregon, 97132
Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org
Charles W. Drescher
- Recruiting
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan, 49120
Site Public Contact, 616-391-1230
Kathleen Y. Butler
- Suspended
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, 49444
- Recruiting
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Philip Kuriakose
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Sami Ibrahimi
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Erin Dean
- Recruiting
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045
Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org
Charles W. Drescher
- Recruiting
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Marc S. Hoffmann
- Recruiting
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Site Public Contact, 215-349-8245, PMCancerResearch@pennmedicine.upenn.edu
Nasheed M. Hossain
- Recruiting
Providence Portland Medical Center
Portland, Oregon, 97213
Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org
Charles W. Drescher
- Recruiting
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Site Public Contact, 503-215-2614, CanRsrchStudies@providence.org
Charles W. Drescher
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Site Public Contact, 503-494-1080, trials@ohsu.edu
Andy I. Chen
- Recruiting
Corewell Health Reed City Hospital
Reed City, Michigan, 49677
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Sneha Purvey
- Recruiting
University of Rochester
Rochester, New York, 14642
Site Public Contact, 585-275-5830
Patrick M. Reagan
- Recruiting
Highlands Oncology Group - Rogers
Rogers, Arkansas, 72758
Site Public Contact, 479-872-8130, research@hogonc.com
Joseph T. Beck
- Recruiting
Dartmouth Cancer Center - North
Saint Johnsbury, Vermont, 05819
Site Public Contact, 800-639-6918, cancer.research.nurse@hitchcock.org
Charles Gaulin
- Recruiting
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Site Public Contact, 877-827-3222
Madhav R. Seshadri
- Recruiting
Swedish Medical Center-First Hill
Seattle, Washington, 98122
Site Public Contact, 206-215-2343, PCRC-NCORP@Swedish.org
Charles W. Drescher
- Recruiting
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672
Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org
Suzanne R. Fanning
- Active, not recruiting
Henry Ford Health Providence Southfield Hospital
Southfield, Michigan, 48075
- Recruiting
Highlands Oncology Group
Springdale, Arkansas, 72762
Site Public Contact, 479-872-8130, research@hogonc.com
Joseph T. Beck
- Recruiting
Munson Medical Center
Traverse City, Michigan, 49684
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
- Recruiting
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
Site Public Contact, UACC-IIT@uacc.arizona.edu
Muhammad Husnain
- Recruiting
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719
Site Public Contact, UACC-IIT@uacc.arizona.edu
Muhammad Husnain
- Recruiting
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301
Site Public Contact, 208-381-2774, eslinget@slhs.org
Charles W. Drescher
- Recruiting
Wilmot Cancer Institute at Webster
Webster, New York, 14580
Site Public Contact, WCICTOresearch@urmc.rochester.edu
Patrick M. Reagan
- Recruiting
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322
Site Public Contact, 313-916-3721, CTOResearch@hfhs.org
Philip Kuriakose
- Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Marc S. Hoffmann
- Recruiting
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Site Public Contact, 570-271-5251, HemonCCTrials@geisinger.edu
Joseph P. Lynch
- Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Site Public Contact, 336-713-6771
Rakhee Vaidya
- Recruiting
Henry Ford Wyandotte Hospital
Wyandotte, Michigan, 48192
Site Public Contact, nhay@hfhs.org
Philip Kuriakose
- Recruiting
University of Michigan Health - West
Wyoming, Michigan, 49519
Site Public Contact, 616-391-1230, crcwm-regulatory@crcwm.org
Kathleen Y. Butler
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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:
- 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.
- Conditions
- Diffuse Large B-Cell Lymphoma, Grade 3b Follicular Lymphoma, Primary Mediastinal (Thymic) Large B-Cell Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Transformed Follic Lymph to Diff Large B-Cell Lymphoma
- Being tested
- Axicabtagene Ciloleucel, Biospecimen Collection, Computed Tomography, Cyclophosphamide, Fludarabine
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Axicabtagene CiloleucelBiological
Also called KTE C19, KTE-C19, KTE-C19 CAR, Yescarta
Given IV
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of blood and tissue samples
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo PET-CT or CT
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
FludarabineDrug
Also called Fluradosa
Given IV
Lisocabtagene MaraleucelBiological
Also called 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, Breyanzi
Given IV
MosunetuzumabBiological
Also called Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A, BTCT 4465A, BTCT-4465A, BTCT4465A
Given IV
Patient ObservationOther
Also called Active Surveillance, deferred therapy, expectant management, Observation
Undergo observation
Polatuzumab VedotinDrug
Also called ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan
Undergo PET-CT
TisagenlecleucelBiological
Also called CART-19, CART19, CTL019, CTL019 T-cells
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Step I (lymphodepleting chemotherapy) | Experimental | 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. Receives: Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Lisocabtagene Maraleucel; Procedure: Positron Emission Tomography; Biological: Tisagenlecleucel |
| Step II Arm I (mosunetuzumab) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Mosunetuzumab; Procedure: Positron Emission Tomography |
| Step II Arm II (polatuzumab vedotin) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Polatuzumab Vedotin; Procedure: Positron Emission Tomography |
| Step II Arm III (polatuzumab vedotin, mosunetuzumab) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Mosunetuzumab; Drug: Polatuzumab Vedotin; Procedure: Positron Emission Tomography |
| Step II Arm IV (observation) | Active comparator | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Patient Observation; Procedure: Positron Emission Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
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.
Measured: From date of randomization to date of first observation of progressive disease or death due to any cause, assessed up to 2 years
Secondary outcomes (5)
Overall survival (OS)
Will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.
Measured: From date of randomization to date of death due to any cause, assessed up to 2 years
Complete remission (CR) conversion rate
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.
Measured: Up to 1 year after randomization
Incidence of adverse events
Measured: Up to 2 years
Association between total metabolic tumor volume (TMTV), standardized uptake value (SUV) max, and sum product (SPD) of diameters
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.
Measured: Up to 2 years
Conversion of CR
Evaluated as a binary variable. Assessed using a univariate logistic regression with a two-sided alpha of 0.05.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2022
- Study start12 Jun 2023
- Primary completion30 Jun 2030 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by SWOG Cancer Research NetworkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 396 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SWOG Cancer Research Network
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Brian T Hess, Principal investigator, SWOG Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05633615
- Sponsor's protocol ID
- S2114
- Other IDs
- NCI-2022-07930, S2114, S2114, U10CA180888
- Status last verified
- Jan 2026
- First submitted
- 21 Nov 2022
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No