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

Status: Recruiting
Location: See all (76) locations...
Intervention Type: Biological, Drug, Procedure, Other
Study Type: Interventional
Study Phase: Phase 2
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 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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

Locations
United States
Arkansas
Highlands Oncology Group - Fayetteville
RECRUITING
Fayetteville
University of Arkansas for Medical Sciences
RECRUITING
Little Rock
Highlands Oncology Group - Rogers
RECRUITING
Rogers
Highlands Oncology Group
RECRUITING
Springdale
Arizona
Banner University Medical Center - Tucson
RECRUITING
Tucson
University of Arizona Cancer Center-North Campus
RECRUITING
Tucson
California
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
RECRUITING
Irvine
UC Irvine Health/Chao Family Comprehensive Cancer Center
RECRUITING
Orange
UCSF Medical Center-Parnassus
RECRUITING
San Francisco
Florida
University of Florida Health Science Center - Gainesville
RECRUITING
Gainesville
Georgia
Emory Saint Joseph's Hospital
RECRUITING
Atlanta
Emory University Hospital/Winship Cancer Institute
RECRUITING
Atlanta
Iowa
University of Iowa/Holden Comprehensive Cancer Center
RECRUITING
Iowa City
Idaho
Saint Luke's Cancer Institute - Boise
RECRUITING
Boise
Saint Luke's Cancer Institute - Fruitland
RECRUITING
Fruitland
Saint Luke's Cancer Institute - Meridian
RECRUITING
Meridian
Saint Luke's Cancer Institute - Nampa
RECRUITING
Nampa
Saint Luke's Cancer Institute - Twin Falls
RECRUITING
Twin Falls
Illinois
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
University of Illinois
RECRUITING
Chicago
Loyola University Medical Center
RECRUITING
Maywood
Kansas
University of Kansas Cancer Center
RECRUITING
Kansas City
University of Kansas Cancer Center-Overland Park
RECRUITING
Overland Park
University of Kansas Hospital-Westwood Cancer Center
RECRUITING
Westwood
Kentucky
The James Graham Brown Cancer Center at University of Louisville
RECRUITING
Louisville
UofL Health Medical Center Northeast
RECRUITING
Louisville
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITING
Baltimore
Michigan
Bronson Battle Creek
RECRUITING
Battle Creek
Wayne State University/Karmanos Cancer Institute
RECRUITING
Detroit
Weisberg Cancer Treatment Center
RECRUITING
Farmington Hills
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
RECRUITING
Grand Rapids
Trinity Health Grand Rapids Hospital
RECRUITING
Grand Rapids
Ascension Borgess Cancer Center
RECRUITING
Kalamazoo
Bronson Methodist Hospital
RECRUITING
Kalamazoo
West Michigan Cancer Center
RECRUITING
Kalamazoo
Trinity Health Muskegon Hospital
RECRUITING
Muskegon
Corewell Health Lakeland Hospitals - Niles Hospital
RECRUITING
Niles
Cancer and Hematology Centers of Western Michigan - Norton Shores
RECRUITING
Norton Shores
Corewell Health Reed City Hospital
RECRUITING
Reed City
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
RECRUITING
Saint Joseph
Henry Ford Health Providence Southfield Hospital
ACTIVE_NOT_RECRUITING
Southfield
Munson Medical Center
RECRUITING
Traverse City
University of Michigan Health - West
RECRUITING
Wyoming
North Carolina
Carolinas Medical Center/Levine Cancer Institute
RECRUITING
Charlotte
Duke University Medical Center
RECRUITING
Durham
Wake Forest University Health Sciences
RECRUITING
Winston-salem
New Mexico
University of New Mexico Cancer Center
RECRUITING
Albuquerque
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING
New York
NYP/Weill Cornell Medical Center
RECRUITING
New York
University of Rochester
RECRUITING
Rochester
Wilmot Cancer Institute at Webster
RECRUITING
Webster
Ohio
Case Western Reserve University
RECRUITING
Cleveland
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Oregon
Providence Newberg Medical Center
RECRUITING
Newberg
Providence Willamette Falls Medical Center
RECRUITING
Oregon City
Oregon Health and Science University
RECRUITING
Portland
Providence Portland Medical Center
RECRUITING
Portland
Providence Saint Vincent Medical Center
RECRUITING
Portland
Pennsylvania
Geisinger Medical Center
RECRUITING
Danville
University of Pennsylvania/Abramson Cancer Center
RECRUITING
Philadelphia
Geisinger Wyoming Valley/Henry Cancer Center
RECRUITING
Wilkes-barre
South Carolina
Prisma Health Cancer Institute - Spartanburg
RECRUITING
Boiling Springs
Medical University of South Carolina
RECRUITING
Charleston
Prisma Health Cancer Institute - Easley
RECRUITING
Easley
Prisma Health Cancer Institute - Butternut
RECRUITING
Greenville
Prisma Health Cancer Institute - Eastside
RECRUITING
Greenville
Prisma Health Cancer Institute - Faris
RECRUITING
Greenville
Prisma Health Cancer Institute - Greer
RECRUITING
Greer
Prisma Health Cancer Institute - Seneca
RECRUITING
Seneca
Tennessee
Baptist Memorial Hospital and Cancer Center-Memphis
RECRUITING
Memphis
Virginia
Virginia Commonwealth University/Massey Cancer Center
RECRUITING
Richmond
Vermont
University of Vermont Medical Center
RECRUITING
Burlington
Wisconsin
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
RECRUITING
Madison
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Medical College of Wisconsin
RECRUITING
Milwaukee
Froedtert and MCW Moorland Reserve Health Center
RECRUITING
New Berlin
Contact Information
Primary
Erin Rogers
erogers@swog.org
210-614-8808
Backup
Dana Sparks
dsparks@swog.org
210-614-8808
Time Frame
Start Date: 2023-06-12
Estimated Completion Date: 2029-12-04
Participants
Target number of participants: 396
Treatments
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.
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.
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.
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.
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.
Sponsors
Collaborators: Genentech, Inc., National Cancer Institute (NCI)
Leads: SWOG Cancer Research Network

This content was sourced from clinicaltrials.gov

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