RECRUITING

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

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 Transformed Marg Zone Lymph to Diff Large B-Cell Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2023-06-12

Study Completion:2029-12-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05633615

Participation Criteria

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

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* STEP 1: REGISTRATION: Participants must have a histologically confirmed diagnosis of diffuse large B-cell lymphoma or follicular lymphoma grade 3b or primary mediastinal large B-cell lymphoma (PMBCL) * STEP 1: REGISTRATION: Participants with transformed DLBCL must have transformed DLBCL from follicular or marginal zone lymphoma * STEP 1: REGISTRATION: Participant must have bi-dimensionally measurable systemic disease (at least one lesion with longest diameter \> 1.5 cm) * STEP 1: REGISTRATION: Participants with secondary central nervous system (CNS) lymphoma (parenchymal, spinal cord, meningeal, cerebrospinal fluid involvement) must be asymptomatic from their CNS disease * STEP 1: REGISTRATION: Participants must be registered for step 1 after they have signed institutional consent for CAR T-cell leukapheresis but prior to the start of lymphodepleting (LD) chemotherapy for commercial CAR T-cell product * STEP 1: REGISTRATION: In the opinion of the enrolling physician, participants must be felt to be a candidate for CAR T-cell therapy with plans to be treated with Food and Drug Administration (FDA) approved commercially available CD19 CAR T-cell construct. * Participants must qualify for commercially approved CD19 CAR T-cell therapy per FDA package insert. * If the CAR T-cell product does not meet parameters to be given as an FDA approved product (i.e. does not meet specification criteria mandated by FDA and is infused under an expanded access protocol \[EAP\] or single participant investigational new drug \[IND\]) the participant will be taken off of study and no longer be eligible for step 2 randomization * STEP 1: REGISTRATION: Participants are permitted to receive or have received 'bridging therapy' after CAR T-cell leukapheresis. However, participants must not receive polatuzumab vedotin, and/or mosunetuzumab as part of bridging therapy. * Bridging therapy is defined as lymphoma directed therapy administered between leukapheresis and the start of LD chemotherapy. This includes cytotoxic chemotherapy (e.g.: bendamustine and rituximab \[BR\], rituximab, gemcitabine and oxaliplatin \[R-gem/ox\]), radiation, corticosteroids, as well as novel therapies such as BTK inhibitors (e.g.: Ibrutinib), immunomodulators (e.g.: lenalidomide), monoclonal antibodies (e.g.: rituximab, obinutuzumab, tafasitamab) antibody drug conjugates (e.g: loncastuximab), checkpoint inhibitors (e.g.: pembrolizumab, nivolumab), clinical trial treatments, etc. * If a participant receives polatuzumab vedotin or mosunetuzumab as bridging they will ineligible to continue on step 1 registration portion of the study and be ineligible for step 2 randomization * STEP 1: REGISTRATION: PET-CT scan must be planned for completion within 60 days prior to the start of LD chemotherapy. * All pre-CAR T-cell therapy disease must be assessed and documented on the baseline/pre-registration tumor assessment form. * If receiving bridging therapy, participants must have a PET-CT scan upon completion of all planned bridging therapy. If the PET-CT scan after completion of bridging therapy is consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization. * Participants are permitted to receive corticosteroids after leukapheresis without the need to repeat a PET-CT scan. If steroids are used, they must be planned to stop no later than 3 days before CAR -T cell infusion. * If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization * STEP 1: REGISTRATION: Participants that have previously been treated with polatuzumab vedotin or mosunetuzumab prior to CAR T-cell leukapheresis for either indolent or aggressive NHL are eligible as long as the participant did not have refractory disease or progression/relapse within 6 months of the last infusion with either agent * STEP 1: REGISTRATION: Participants must be planning to receive CAR T-cell infusion no earlier than 2 days and no later than 14 days after completion of the last day of lymphodepleting chemotherapy. Any participant receiving CAR T-cell infusion outside of this window will be ineligible for step 2 randomization * STEP 1: REGISTRATION: LD chemotherapy prior to CAR T-cell infusion must be planned to start within 60 days after step 1 registration * STEP 1: REGISTRATION: Participants must be \>= 18 years of age at the time of registration * STEP 1: REGISTRATION: Participants must have Zubrod performance score (PS) of 0, 1, or 2 * STEP 1: REGISTRATION: Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (within 14 days prior to registration) * Unless due to Gilbert's disease or lymphomatous involvement of liver * STEP 1: REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 14 days prior to registration) * STEP 1: REGISTRATION: Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 14 days prior to registration. Estimated creatinine clearance is based on actual body weight * STEP 1: REGISTRATION: Participants must have an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 60 days prior to registration with a cardiac ejection fraction \>= 40%. * Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better. * Participants must not have documented myocardial infarction and percutaneous coronary intervention (PCI) within 6 months prior to registration or myocardial infarction without PCI within 3 months of registration, or unstable angina * STEP 1: REGISTRATION: Participants with peripheral neuropathy must have \< grade 2 * STEP 1: REGISTRATION: Participants with hepatitis B virus infection must have undetectable viral load within 14 days prior to registration, be on suppressive therapy and have no evidence of hepatitis B virus (HBV) related hepatic damage * STEP 1: REGISTRATION: Participants with hepatitis C infection must have eradication therapy completed, have no evidence of hepatitis C infection (HCV) related damage and have undetectable viral load within 14 days prior to registration * STEP 1: REGISTRATION: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration * STEP 1: REGISTRATION: Participants must be offered the opportunity to participate in banking for planned translational medicine and future research. With participant consent, any residuals from the mandatory tissue submission will also be banked for future research. * Note: Streck tubes must be ordered in advance. Please allow 5-7 days for shipment of the collection kits * STEP 1: REGISTRATION: NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system. * Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. * For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations * STEP 2: RANDOMIZATION: Participants must have met all eligibility criteria for step 1 registration * STEP 2: RANDOMIZATION: Participant's CAR T-cell product must have met specification parameters to be given as an FDA approved commercial product * STEP 2: RANDOMIZATION: Participants must have a PET-CT scan between days 25-40 after CAR T-cell infusion and determined to have a response consistent with stable disease or partial remission by central review compared to most recent pre-LD chemo/CAR T-cell PET-CT scan. * Note: Patients with delayed enrollment \> 21 days after 'day +30' PET-CT scan will necessitate a repeat PET-CT scan if concerning signs or symptoms of lymphoma progression develop. * Note: If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization * STEP 2: RANDOMIZATION: Eligible participants must be randomized no later than 60 days after CAR -T infusion * STEP 2: RANDOMIZATION: Participants must have started LD chemotherapy within 60 days of signing consent for step 1 registration * STEP 2: RANDOMIZATION: Participants must have S2114 CAR T-cell therapy form submitted to Southwest Oncology Group (SWOG) prior to step 2 randomization * STEP 2: RANDOMIZATION: Participants must have had a PET-CT scan upon completion of all planned bridging therapy if received, with the exception of up to 7 days of corticosteroids. If the PET-CT scan after completion of bridging therapy was consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization. * If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization * STEP 2: RANDOMIZATION: Participants must have Zubrod PS of 0, 1, or 2 * STEP 2: RANDOMIZATION: Absolute neutrophil count (ANC) \>= 1.0 x 10\^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization) * STEP 2: RANDOMIZATION: Platelets \>= 75 x 10\^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization) * STEP 2: RANDOMIZATION: Total bilirubin =\< 2 x institutional ULN (within 7 days prior to step 2 randomization) * Unless due to Gilbert's disease or lymphomatous involvement of liver * STEP 2: RANDOMIZATION: AST and ALT =\< 3 x institutional ULN (within 7 days prior to step 2 randomization) * STEP 2: RANDOMIZATION: Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 7 days prior to step 2 randomization. Estimated creatinine clearance is based on actual body weight (within 7 days prior to step 2 randomization) * STEP 2: RANDOMIZATION: Participants with peripheral neuropathy must have \< grade 2 * STEP 2: RANDOMIZATION: Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better * STEP 2: RANDOMIZATION: Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 2 randomization and on suppressive therapy * STEP 2: RANDOMIZATION: Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 2 randomization * STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be continuing to receive anti-retroviral therapy and have an undetectable viral load test within 14 days prior to step 2 randomization * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have documented disease progression while on Arm 4 (observation) on this protocol. The follow-up tumor assessment form documenting disease progression must be submitted to SWOG prior to step 3 crossover registration * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must be registered within 28 days of the date of progression * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have imaging that clearly demonstrates progression compared to day +30 PET-CT scan * Note: These scans should be performed as standard of care and only performed between scheduled response assessments required for study if symptoms arise that are concerning for progression * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have Zubrod PS of 0, 1, or 2 * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): ANC \>= 1.0 x 10\^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration) * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Platelets \>= 75 x 10\^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration) * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Total bilirubin =\< 2 x institutional ULN (within 14 days prior to step 3 crossover registration) * Unless due to Gilbert's disease or lymphomatous involvement of liver * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): AST and ALT =\< 3 x institutional ULN * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within days prior to step 3 crossover registration. Estimated creatinine clearance is based on actual body weight (within 14 days prior to step 3 crossover registration) * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with peripheral neuropathy must have \< grade 2 * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration and on suppressive therapy * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration * STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with known human immunodefici	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* STEP 1: REGISTRATION: Participants must have a histologically confirmed diagnosis of diffuse large B-cell lymphoma or follicular lymphoma grade 3b or primary mediastinal large B-cell lymphoma (PMBCL)
* STEP 1: REGISTRATION: Participants with transformed DLBCL must have transformed DLBCL from follicular or marginal zone lymphoma
* STEP 1: REGISTRATION: Participant must have bi-dimensionally measurable systemic disease (at least one lesion with longest diameter \> 1.5 cm)
* STEP 1: REGISTRATION: Participants with secondary central nervous system (CNS) lymphoma (parenchymal, spinal cord, meningeal, cerebrospinal fluid involvement) must be asymptomatic from their CNS disease
* STEP 1: REGISTRATION: Participants must be registered for step 1 after they have signed institutional consent for CAR T-cell leukapheresis but prior to the start of lymphodepleting (LD) chemotherapy for commercial CAR T-cell product
* STEP 1: REGISTRATION: In the opinion of the enrolling physician, participants must be felt to be a candidate for CAR T-cell therapy with plans to be treated with Food and Drug Administration (FDA) approved commercially available CD19 CAR T-cell construct.
* Participants must qualify for commercially approved CD19 CAR T-cell therapy per FDA package insert.
* If the CAR T-cell product does not meet parameters to be given as an FDA approved product (i.e. does not meet specification criteria mandated by FDA and is infused under an expanded access protocol \[EAP\] or single participant investigational new drug \[IND\]) the participant will be taken off of study and no longer be eligible for step 2 randomization
* STEP 1: REGISTRATION: Participants are permitted to receive or have received 'bridging therapy' after CAR T-cell leukapheresis. However, participants must not receive polatuzumab vedotin, and/or mosunetuzumab as part of bridging therapy.
* Bridging therapy is defined as lymphoma directed therapy administered between leukapheresis and the start of LD chemotherapy. This includes cytotoxic chemotherapy (e.g.: bendamustine and rituximab \[BR\], rituximab, gemcitabine and oxaliplatin \[R-gem/ox\]), radiation, corticosteroids, as well as novel therapies such as BTK inhibitors (e.g.: Ibrutinib), immunomodulators (e.g.: lenalidomide), monoclonal antibodies (e.g.: rituximab, obinutuzumab, tafasitamab) antibody drug conjugates (e.g: loncastuximab), checkpoint inhibitors (e.g.: pembrolizumab, nivolumab), clinical trial treatments, etc.
* If a participant receives polatuzumab vedotin or mosunetuzumab as bridging they will ineligible to continue on step 1 registration portion of the study and be ineligible for step 2 randomization
* STEP 1: REGISTRATION: PET-CT scan must be planned for completion within 60 days prior to the start of LD chemotherapy.
* All pre-CAR T-cell therapy disease must be assessed and documented on the baseline/pre-registration tumor assessment form.
* If receiving bridging therapy, participants must have a PET-CT scan upon completion of all planned bridging therapy. If the PET-CT scan after completion of bridging therapy is consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization.
* Participants are permitted to receive corticosteroids after leukapheresis without the need to repeat a PET-CT scan. If steroids are used, they must be planned to stop no later than 3 days before CAR -T cell infusion.
* If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 1: REGISTRATION: Participants that have previously been treated with polatuzumab vedotin or mosunetuzumab prior to CAR T-cell leukapheresis for either indolent or aggressive NHL are eligible as long as the participant did not have refractory disease or progression/relapse within 6 months of the last infusion with either agent
* STEP 1: REGISTRATION: Participants must be planning to receive CAR T-cell infusion no earlier than 2 days and no later than 14 days after completion of the last day of lymphodepleting chemotherapy. Any participant receiving CAR T-cell infusion outside of this window will be ineligible for step 2 randomization
* STEP 1: REGISTRATION: LD chemotherapy prior to CAR T-cell infusion must be planned to start within 60 days after step 1 registration
* STEP 1: REGISTRATION: Participants must be \>= 18 years of age at the time of registration
* STEP 1: REGISTRATION: Participants must have Zubrod performance score (PS) of 0, 1, or 2
* STEP 1: REGISTRATION: Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 1: REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 14 days prior to registration)
* STEP 1: REGISTRATION: Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 14 days prior to registration. Estimated creatinine clearance is based on actual body weight
* STEP 1: REGISTRATION: Participants must have an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 60 days prior to registration with a cardiac ejection fraction \>= 40%.
* Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better.
* Participants must not have documented myocardial infarction and percutaneous coronary intervention (PCI) within 6 months prior to registration or myocardial infarction without PCI within 3 months of registration, or unstable angina
* STEP 1: REGISTRATION: Participants with peripheral neuropathy must have \< grade 2
* STEP 1: REGISTRATION: Participants with hepatitis B virus infection must have undetectable viral load within 14 days prior to registration, be on suppressive therapy and have no evidence of hepatitis B virus (HBV) related hepatic damage
* STEP 1: REGISTRATION: Participants with hepatitis C infection must have eradication therapy completed, have no evidence of hepatitis C infection (HCV) related damage and have undetectable viral load within 14 days prior to registration
* STEP 1: REGISTRATION: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* STEP 1: REGISTRATION: Participants must be offered the opportunity to participate in banking for planned translational medicine and future research. With participant consent, any residuals from the mandatory tissue submission will also be banked for future research.
* Note: Streck tubes must be ordered in advance. Please allow 5-7 days for shipment of the collection kits
* STEP 1: REGISTRATION: NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* STEP 2: RANDOMIZATION: Participants must have met all eligibility criteria for step 1 registration
* STEP 2: RANDOMIZATION: Participant's CAR T-cell product must have met specification parameters to be given as an FDA approved commercial product
* STEP 2: RANDOMIZATION: Participants must have a PET-CT scan between days 25-40 after CAR T-cell infusion and determined to have a response consistent with stable disease or partial remission by central review compared to most recent pre-LD chemo/CAR T-cell PET-CT scan.
* Note: Patients with delayed enrollment \> 21 days after 'day +30' PET-CT scan will necessitate a repeat PET-CT scan if concerning signs or symptoms of lymphoma progression develop.
* Note: If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 2: RANDOMIZATION: Eligible participants must be randomized no later than 60 days after CAR -T infusion
* STEP 2: RANDOMIZATION: Participants must have started LD chemotherapy within 60 days of signing consent for step 1 registration
* STEP 2: RANDOMIZATION: Participants must have S2114 CAR T-cell therapy form submitted to Southwest Oncology Group (SWOG) prior to step 2 randomization
* STEP 2: RANDOMIZATION: Participants must have had a PET-CT scan upon completion of all planned bridging therapy if received, with the exception of up to 7 days of corticosteroids. If the PET-CT scan after completion of bridging therapy was consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization.
* If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 2: RANDOMIZATION: Participants must have Zubrod PS of 0, 1, or 2
* STEP 2: RANDOMIZATION: Absolute neutrophil count (ANC) \>= 1.0 x 10\^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Platelets \>= 75 x 10\^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Total bilirubin =\< 2 x institutional ULN (within 7 days prior to step 2 randomization)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 2: RANDOMIZATION: AST and ALT =\< 3 x institutional ULN (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 7 days prior to step 2 randomization. Estimated creatinine clearance is based on actual body weight (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Participants with peripheral neuropathy must have \< grade 2
* STEP 2: RANDOMIZATION: Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* STEP 2: RANDOMIZATION: Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 2 randomization and on suppressive therapy
* STEP 2: RANDOMIZATION: Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 2 randomization
* STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be continuing to receive anti-retroviral therapy and have an undetectable viral load test within 14 days prior to step 2 randomization
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have documented disease progression while on Arm 4 (observation) on this protocol. The follow-up tumor assessment form documenting disease progression must be submitted to SWOG prior to step 3 crossover registration
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must be registered within 28 days of the date of progression
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have imaging that clearly demonstrates progression compared to day +30 PET-CT scan
* Note: These scans should be performed as standard of care and only performed between scheduled response assessments required for study if symptoms arise that are concerning for progression
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have Zubrod PS of 0, 1, or 2
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): ANC \>= 1.0 x 10\^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Platelets \>= 75 x 10\^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Total bilirubin =\< 2 x institutional ULN (within 14 days prior to step 3 crossover registration)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): AST and ALT =\< 3 x institutional ULN
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within days prior to step 3 crossover registration. Estimated creatinine clearance is based on actual body weight (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with peripheral neuropathy must have \< grade 2
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration and on suppressive therapy
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with known human immunodefici

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Kat Gasic

CONTACT

210-614-8808

kgasic@swog.org

Dana Sparks

CONTACT

210-614-8808

dsparks@swog.org

Principal Investigator

Brian T Hess

PRINCIPAL_INVESTIGATOR

SWOG Cancer Research Network

Study Locations (Sites)

Banner University Medical Center - Tucson

Tucson, Arizona, 85719

United States

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719

United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868

United States

UCSF Medical Center-Parnassus

San Francisco, California, 94143

United States

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342

United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712

United States

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, 83619

United States

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, 83642

United States

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, 83686

United States

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho, 83301

United States

University of Illinois

Chicago, Illinois, 60612

United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637

United States

Loyola University Medical Center

Maywood, Illinois, 60153

United States

University of Kansas Cancer Center

Kansas City, Kansas, 66160

United States

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210

United States

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205

United States

Bronson Battle Creek

Battle Creek, Michigan, 49017

United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334

United States

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, 49503

United States

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, 49503

United States

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007

United States

West Michigan Cancer Center

Kalamazoo, Michigan, 49007

United States

Ascension Borgess Cancer Center

Kalamazoo, Michigan, 49009

United States

Trinity Health Muskegon Hospital

Muskegon, Michigan, 49444

United States

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan, 49444

United States

Corewell Health Reed City Hospital

Reed City, Michigan, 49677

United States

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

Saint Joseph, Michigan, 49085

United States

Ascension Providence Hospitals - Southfield

Southfield, Michigan, 48075

United States

Munson Medical Center

Traverse City, Michigan, 49684

United States

University of Michigan Health - West

Wyoming, Michigan, 49519

United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87102

United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032

United States

University of Rochester

Rochester, New York, 14642

United States

Wilmot Cancer Institute at Webster

Webster, New York, 14580

United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157

United States

Case Western Reserve University

Cleveland, Ohio, 44106

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

United States

Providence Newberg Medical Center

Newberg, Oregon, 97132

United States

Providence Willamette Falls Medical Center

Oregon City, Oregon, 97045

United States

Providence Portland Medical Center

Portland, Oregon, 97213

United States

Providence Saint Vincent Medical Center

Portland, Oregon, 97225

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

Geisinger Medical Center

Danville, Pennsylvania, 17822

United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

United States

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, 18711

United States

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, 29316

United States

Medical University of South Carolina

Charleston, South Carolina, 29425

United States

Prisma Health Cancer Institute - Easley

Easley, South Carolina, 29640

United States

Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, 29605

United States

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, 29605

United States

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, 29615

United States

Prisma Health Cancer Institute - Greer

Greer, South Carolina, 29650

United States

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, 29672

United States

Baptist Memorial Hospital and Cancer Center-Memphis

Memphis, Tennessee, 38120

United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298

United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792

United States

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Froedtert and MCW Moorland Reserve Health Center

New Berlin, Wisconsin, 53151

United States

Collaborators and Investigators

Sponsor: SWOG Cancer Research Network

Brian T Hess, PRINCIPAL_INVESTIGATOR, SWOG Cancer Research Network

Study Record Dates

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

Study Registration Dates

Study Start Date2023-06-12

Study Completion Date2029-12-04

Study Record Updates

Study Start Date2023-06-12

Study Completion Date2029-12-04

Terms related to this study

Additional Relevant MeSH Terms

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