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

Recruiting now · Phase 2

Conditions studied: 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, Transformed Marg Zone Lymph to Diff Large B-Cell Lymphoma

In brief

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.

Key facts

Study ID

NCT05633615

Run by

SWOG Cancer Research Network

People needed

396

Starts

2023-06-12

Expected to finish

2030-06-30

Last updated by the study team

2026-02-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

Where it is running

• Banner University Medical Center - Tucson — Tucson, Arizona, United States (enrolling)
• Highlands Oncology Group - Fayetteville — Fayetteville, Arkansas, United States (enrolling)
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (enrolling)
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States (enrolling)
• Highlands Oncology Group — Springdale, Arkansas, United States (enrolling)
• UC Irvine Health Cancer Center-Newport — Costa Mesa, California, United States (enrolling)
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care — Irvine, California, United States (enrolling)
• UCI Health Laguna Hills — Laguna Hills, California, United States (enrolling)
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States (enrolling)
• Highlands Oncology Group - Rogers — Rogers, Arkansas, United States (enrolling)
• UF Health Cancer Institute - Gainesville — Gainesville, Florida, United States (enrolling)
• Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States (enrolling)
• Emory Saint Joseph's Hospital — Atlanta, Georgia, United States (enrolling)
• Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Fruitland — Fruitland, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Meridian — Meridian, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Nampa — Nampa, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Twin Falls — Twin Falls, Idaho, United States (enrolling)
• University of Illinois — Chicago, Illinois, United States (enrolling)
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States (enrolling)
• UCSF Medical Center-Parnassus — San Francisco, California, United States (enrolling)
• University of Iowa/Holden Comprehensive Cancer Center — Iowa City, Iowa, United States (enrolling)
• University of Kansas Cancer Center — Kansas City, Kansas, United States (enrolling)
• University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States (enrolling)
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States (enrolling)

Full record on ClinicalTrials.gov

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