Testing Drug Treatments after CAR T-cell Therapy in Patients with Diffuse Large B-cell Lymphoma That Has Come Back or Not Responded to Treatment
Trial Status: active
This phase II trial tests how mosunetuzumab with or without polatuzumab vedotin works in treating patients undergoing chemotherapy followed by chimeric antigen receptor (CAR) T-cell therapy for diffuse large B-cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory) or in patients with grade IIIB follicular lymphoma. Mosunetuzumab is a monoclonal antibody that binds to a protein called CD3, which is found on T cells (a type of white blood cell). It also binds to a protein called CD20, which is found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Polatuzumab vedotin is a monoclonal antibody called polatuzumab, linked to an anticancer drug called vedotin. Polatuzumab vedotin attaches to specific molecules (receptors) called CD79B, which is found on B cells and some lymphoma cells and delivers vedotin to kill them. It is a form of targeted therapy and a type of antibody-drug conjugate. Fludarabine is in a class of medications called purine analogs. It stops cells from making DNA and may kill cancer cells. It is a type of antimetabolite. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell’s DNA and may kill cancer cells. It may also lower the body’s immune response. CAR T-cell therapy is a type of treatment in which a patient's T cells 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 with or without polatuzumab vedotin after chemotherapy and CAR T-cell therapy may be more effective at controlling or shrinking relapsed/refractory diffuse large B-cell lymphoma or grade IIIB follicular lymphoma than not giving them.
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. * 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. * Participants are permitted to receive polatuzumab vedotin as part of bridging therapy. However, participants that have progression of disease after receipt of polatuzumab vedotin as bridging therapy will be ineligible for step 1 registration * Participants are not permitted to receive mosunetuzumab as bridging therapy. Participants are permitted to receive other CD20 bispecific T-cell engager therapies other than mosunetuzumab (ie glofitamab, epcoritamab) as part of bridging therapy. However, participants that have progression of disease after receipt of CD20 bi-specific T-cell engager as bridging therapy will be ineligible for step 1 registration.
- 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. If participants receive polatuzumab vedotin or CD20 Bi-specific T-cell engager as bridging therapy and PET-CT scan after completion is consistent with complete remission or progression of disease per Lugano criteria as determined by the enrolling physician, that participant will be ineligible for step 1 registration * 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. Recommend dose no greater than dexamethasone 40 mg (or equivalent) for < 7 days. * 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 and/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 =< 1.5 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 must not have peripheral neuropathy that affects activities of daily living 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: 2. Participants who can complete questionnaires in English, or Spanish, must be offered the opportunity to participate in the patient-reported outcomes (PRO-CTCAE) study. However, participation in the patient-reported outcomes study is optional for participants. NOTE: Participants enrolled to S2114 prior to Revision #2 are not eligible for the quality of life (QOL)
- 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 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 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 the PET-CT scan after completion of bridging therapy with polatuzumab vedotin or CD20 Bi-specific T-cell engager therapy is consistent with complete remission or progression of disease by Lugano criteria as determined by the 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 =< 1.5 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 must not have peripheral neuropathy that affects activities of daily living
- 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 =< 1.5 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 must not have peripheral neuropathy that affects activities of daily living
- 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 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 3 crossover registration
Exclusion Criteria
- STEP 1: REGISTRATION: Participants must not have a history of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), a diagnosis of Richter's transformation, or a diagnosis of mantle cell lymphoma
- STEP 1: REGISTRATION: Participants must not have received prior CAR T-cell infusion previous to step 1 registration
- STEP 1: REGISTRATION: Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
- STEP 1: REGISTRATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of the investigational regimen
- STEP 1: REGISTRATION: Participants must not have any evidence of serious intracranial hemorrhage and/or edema within 6 months prior to registration
- STEP 1: REGISTRATION: Participants must not have evidence of acute or chronic graft vs host disease from allogeneic stem cell transplant unless it is either grade 1 involvement of the skin requiring topical therapy or not requiring systemic immunosuppression
- STEP 1: REGISTRATION: Participants must not have known or suspected hypersensitivity to any of the study agents
- STEP 1: REGISTRATION: Participants must not have active autoimmune disease requiring systemic treatment in the last 2 years
- STEP 2: RANDOMIZATION: Participants must not have received CAR T-cell products given via expanded access protocol (EAP) or under single participant investigational new drug (IND)
- STEP 2: RANDOMIZATION: Participants must not have clinical evidence of active CNS lymphoma involvement. This includes parenchymal, spinal cord, meningeal, or cerebrospinal fluid involvement. * Note: Participants that had cerebrospinal fluid involvement at step 1 registration must submit documentation illustrating remission as assessed by CSF evaluation within 28 days prior to registration. * Note: Participants with history of parenchymal, spinal cord, or meningeal CNS involvement at step 1 registration must submit documentation illustrating remission as assessed by contrast-enhanced MRI imaging within 28 days prior to registration
- STEP 2: RANDOMIZATION: Participants must have received an FDA approved CD19 CAR T-cell construct no earlier than 2 days and no later than 14 days after completion of the last day of lymphodepleting chemotherapy.
- STEP 2: RANDOMIZATION: Participants must not have received radiation or chemotherapy since CAR T-cell infusion and there must be no intention to send the participant for receipt of radiation therapy after randomization
- STEP 2: RANDOMIZATION: Participants must not have documented myocardial infarction or unstable angina since step 1 registration
- STEP 2: RANDOMIZATION: Participants must not have any evidence of cytokine release syndrome (CRS) by American Society for Transplantation and Cellular Therapy (ASTCT) guidelines within 7 days prior to step 2 randomization. Corticosteroid doses for treatment of CRS no higher than 10 mg of prednisone (or equivalent) are allowed if deemed to be part of a taper or replacement therapy (i.e. adrenal insufficiency or pituitary insufficiency) by the investigator
- STEP 2: RANDOMIZATION: Participants must not have evidence of I-CANS by ASTCT guidelines within 7 days prior to step 2 randomization. Corticosteroid doses for treatment of I-CANS no higher than 10 mg of prednisone (or equivalent) are allowed if deemed to be part of a taper or replacement therapy (i.e. adrenal insufficiency or pituitary insufficiency) by the investigator
- STEP 2: RANDOMIZATION: Participants must not have any evidence of serious intracranial hemorrhage and/or edema since step 1 registration
- STEP 2: RANDOMIZATION: Participants must not have uncontrolled systemic fungal, bacterial or viral infection
- STEP 2: RANDOMIZATION: Participants must not have known or suspected chronic active Epstein-Barr virus (EBV) infection
- STEP 2: RANDOMIZATION: Participants must not have known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
- STEP 2: RANDOMIZATION: Participants must not have history of progressive multifocal leukoencephalopathy (PML)
- STEP 2: RANDOMIZATION: Participants must not have active autoimmune disease requiring systemic treatment since enrollment to step 1 registration
- STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must not have received any lymphoma directed therapy (systemic therapy, radiation) after progression and prior to step 3 crossover registration
- STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must not have documented myocardial infarction or unstable angina since step 2 randomization
- STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must not have any evidence of serious intracranial hemorrhage and/or edema since step 2 randomization
- STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must not have uncontrolled systemic fungal, bacterial or viral infection
Additional locations may be listed on ClinicalTrials.gov for NCT05633615.
Locations matching your search criteria
United States
Arizona
Tucson
University of Arizona Cancer Center-North Campus
Status: Active
Contact: Site Public Contact
Email: UACC-IIT@uacc.arizona.edu
Banner University Medical Center - Tucson
Status: Active
Contact: Site Public Contact
Email: UACC-IIT@uacc.arizona.edu
Arkansas
Fayetteville
Highlands Oncology Group - Fayetteville
Status: Active
Contact: Site Public Contact
Phone: 479-872-8100
Email: research@hogonc.com
Little Rock
University of Arkansas for Medical Sciences
Status: Active
Contact: Site Public Contact
Phone: 501-686-8274
Rogers
Highlands Oncology Group - Rogers
Status: Active
Contact: Site Public Contact
Phone: 479-872-8130
Email: research@hogonc.com
Springdale
Highlands Oncology Group
Status: Active
Contact: Site Public Contact
Phone: 479-872-8130
Email: research@hogonc.com
California
Costa Mesa
UC Irvine Health Cancer Center-Newport
Status: Active
Contact: Site Public Contact
Phone: 877-827-8839
Irvine
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Status: Active
Contact: Site Public Contact
Phone: 877-827-8839
Email: ucstudy@uci.edu
Laguna Hills
UCI Health Laguna Hills
Status: Active
Contact: Site Public Contact
Phone: 877-827-8839
Email: ucstudy@uci.edu
Orange
UC Irvine Health/Chao Family Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 877-827-8839
Email: ucstudy@uci.edu
San Francisco
UCSF Medical Center-Parnassus
Status: Active
Contact: Site Public Contact
Phone: 877-827-3222
Florida
Gainesville
University of Florida Health Science Center - Gainesville
Status: Active
Contact: Site Public Contact
Phone: 352-273-8010
Email: cancer-center@ufl.edu
Georgia
Atlanta
Emory University Hospital/Winship Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 404-778-1868
Emory Saint Joseph's Hospital
Status: Active
Contact: Site Public Contact
Phone: 404-851-7115
Idaho
Boise
Saint Luke's Cancer Institute - Boise
Status: Active
Contact: Site Public Contact
Phone: 208-381-2774
Email: eslinget@slhs.org
Fruitland
Saint Luke's Cancer Institute - Fruitland
Status: Active
Contact: Site Public Contact
Phone: 208-381-2774
Email: eslinget@slhs.org
Meridian
Saint Luke's Cancer Institute - Meridian
Status: Active
Contact: Site Public Contact
Phone: 208-381-2774
Email: eslinget@slhs.org
Nampa
Saint Luke's Cancer Institute - Nampa
Status: Active
Contact: Site Public Contact
Phone: 208-381-2774
Email: eslinget@slhs.org
Twin Falls
Saint Luke's Cancer Institute - Twin Falls
Status: Active
Contact: Site Public Contact
Phone: 208-381-2774
Email: eslinget@slhs.org
Illinois
Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 773-702-8222
University of Illinois
Status: Active
Contact: Site Public Contact
Phone: 312-355-3046
Maywood
Loyola University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 708-226-4357
Iowa
Iowa City
University of Iowa/Holden Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-237-1225
Kansas
Kansas City
University of Kansas Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 913-588-3671
Email: KUCC_Navigation@kumc.edu
Overland Park
University of Kansas Cancer Center-Overland Park
Status: Active
Contact: Site Public Contact
Phone: 913-588-3671
Email: KUCC_Navigation@kumc.edu
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 913-588-3671
Email: KUCC_Navigation@kumc.edu
Kentucky
Louisville
UofL Health Medical Center Northeast
Status: Active
Contact: Site Public Contact
Phone: 502-852-2755
Email: ctoinfo@louisville.edu
The James Graham Brown Cancer Center at University of Louisville
Status: Active
Contact: Site Public Contact
Phone: 502-562-3429
Maryland
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 410-955-8804
Email: jhcccro@jhmi.edu
University of Maryland/Greenebaum Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-888-8823
Michigan
Battle Creek
Bronson Battle Creek
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Detroit
Wayne State University/Karmanos Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Farmington Hills
Weisberg Cancer Treatment Center
Status: Active
Contact: Site Public Contact
Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Grand Rapids
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Trinity Health Grand Rapids Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Kalamazoo
West Michigan Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Bronson Methodist Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Beacon Kalamazoo Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 574-647-7370
Muskegon
Trinity Health Muskegon Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Niles
Corewell Health Lakeland Hospitals - Niles Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Norton Shores
Cancer and Hematology Centers of Western Michigan - Norton Shores
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: connie.szczepanek@crcwm.org
Reed City
Corewell Health Reed City Hospital
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Saint Joseph
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Traverse City
Munson Medical Center
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Wyoming
University of Michigan Health - West
Status: Active
Contact: Site Public Contact
Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
New Hampshire
Lebanon
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 800-639-6918
New Mexico
Albuquerque
University of New Mexico Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 505-925-0348
New York
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 212-342-5162
NYP/Weill Cornell Medical Center
Status: Active
Contact: Site Public Contact
Phone: 212-746-1848
Rochester
University of Rochester
Status: Active
Contact: Site Public Contact
Phone: 585-275-5830
Webster
Wilmot Cancer Institute at Webster
Status: Active
Contact: Site Public Contact
North Carolina
Charlotte
Carolinas Medical Center/Levine Cancer Institute
Status: Active
Contact: Site Public Contact
Phone: 800-804-9376
Concord
Atrium Health Cabarrus/LCI-Concord
Status: Active
Contact: Site Public Contact
Phone: 800-804-9376
Durham
Duke University Medical Center
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 888-275-3853
Winston-Salem
Wake Forest University Health Sciences
Status: Active
Contact: Site Public Contact
Phone: 336-713-6771
North Dakota
Fargo
Sanford Roger Maris Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 701-234-6161
Sanford Broadway Medical Center
Status: Active
Contact: Site Public Contact
Phone: 701-323-5760
Ohio
Cleveland
Case Western Reserve University
Status: Active
Contact: Site Public Contact
Phone: 800-641-2422
Email: CTUReferral@UHhospitals.org
Oklahoma
Oklahoma City
University of Oklahoma Health Sciences Center
Status: Active
Contact: Site Public Contact
Phone: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu
Oregon
Newberg
Providence Newberg Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Oregon City
Providence Willamette Falls Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Portland
Providence Saint Vincent Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Providence Portland Medical Center
Status: Active
Contact: Site Public Contact
Phone: 503-215-2614
Oregon Health and Science University
Status: Active
Contact: Site Public Contact
Phone: 503-494-1080
Email: trials@ohsu.edu
Pennsylvania
Danville
Geisinger Medical Center
Status: Active
Contact: Site Public Contact
Phone: 570-271-5251
Email: HemonCCTrials@geisinger.edu
Philadelphia
University of Pennsylvania/Abramson Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 215-349-8245
Wilkes-Barre
Geisinger Wyoming Valley/Henry Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 570-271-5251
Email: HemonCCTrials@geisinger.edu
South Carolina
Boiling Springs
Prisma Health Cancer Institute - Spartanburg
Status: Active
Contact: Site Public Contact
Phone: 864-522-4317
Charleston
Medical University of South Carolina
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 843-792-9321
Email: hcc-clinical-trials@musc.edu
Easley
Prisma Health Cancer Institute - Easley
Status: Active
Contact: Site Public Contact
Phone: 864-522-4317
Greenville
Prisma Health Cancer Institute - Butternut
Status: Active
Contact: Site Public Contact
Phone: 864-522-4317
Prisma Health Cancer Institute - Eastside
Status: Active
Contact: Site Public Contact
Phone: 864-522-4317
Prisma Health Cancer Institute - Faris
Status: Active
Contact: Site Public Contact
Phone: 864-522-4317
Greer
Prisma Health Cancer Institute - Greer
Status: Active
Contact: Site Public Contact
Phone: 864-522-4317
Seneca
Prisma Health Cancer Institute - Seneca
Status: Active
Contact: Site Public Contact
Phone: 864-522-4317
Tennessee
Memphis
Baptist Memorial Hospital and Cancer Center-Memphis
Status: Active
Contact: Site Public Contact
Phone: 901-226-1366
Email: BCCclintrials@bmhcc.org
Vermont
Burlington
University of Vermont Medical Center
Status: Active
Contact: Site Public Contact
Phone: 802-656-4101
Email: rpo@uvm.edu
University of Vermont and State Agricultural College
Status: Active
Contact: Site Public Contact
Phone: 802-656-8990
Email: rpo@uvm.edu
Saint Johnsbury
Dartmouth Cancer Center - North
Status: Active
Contact: Site Public Contact
Phone: 800-639-6918
Virginia
Richmond
VCU Massey Comprehensive Cancer Center
Status: Active
Contact: Site Public Contact
Phone: 804-628-6430
Email: CTOclinops@vcu.edu
Washington
Seattle
Swedish Medical Center-First Hill
Status: Active
Contact: Site Public Contact
Phone: 206-215-2343
Email: PCRC-NCORP@Swedish.org
Wisconsin
Madison
University of Wisconsin Carbone Cancer Center - University Hospital
Status: Active
Contact: Site Public Contact
Phone: 800-622-8922
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Status: Active
Contact: Site Public Contact
Phone: 800-622-8922
Milwaukee
Medical College of Wisconsin
Status: Active
Contact: Site Public Contact
Phone: 414-805-3666
New Berlin
Froedtert and MCW Moorland Reserve Health Center
Status: Active
Contact: Site Public Contact
Phone: 414-805-0505
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. 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.
PATIENT REPORTED OUTCOME-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE) OBJECTIVE:
I. To compare the incidence and severity of selected patient-reported symptomatic adverse events using PRO-CTCAE items between patients randomized to arms 1-4.
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 days 1-3. Patients then receive tisagenlecleucel IV between days 6-15, axicabtagene ciloleucel IV on day 6 or lisocabtagene maraleucel IV between days 6-11. Patients also undergo PET-CT imaging.
STEP II: Patients are randomized to 1 of 4 arms.
ARM I: Patients receive mosunetuzumab IV over 2-4 hours on days 1, 8, and 15 of cycle 1, followed by day 1 of each subsequent cycle. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET-CT or CT imaging and collection of blood and tissue samples throughout the study.
ARM II: Patients receive polatuzumab vedotin IV per institutional guidelines on day 1 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET-CT or CT imaging and collection of blood and tissue samples throughout the study.
ARM III: Patients receive polatuzumab vedotin IV per institutional guidelines on day 1 of cycles 2-7 and mosunetuzumab IV over 2-4 hours on days 1, 8, and 15 of cycle 1, followed by day 1 of each subsequent cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo PET-CT or CT imaging and collection of blood and tissue samples throughout the study.
ARM IV: Patients undergo observation over 90 minutes. Patients also undergo PET-CT or CT imaging and 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.
After completion of study treatment, patients who receive CAR T-cell infusion and who are ineligible for Step 2 randomization will be followed every 3 months for 2 years, then every 6 months until 5 years after Step 1 registration, or progression, or death, whichever occurs first.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationSWOG
Principal InvestigatorBrian Timothy Hess
- Primary IDS2114
- Secondary IDsNCI-2022-07930
- ClinicalTrials.gov IDNCT05633615