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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Axicabtagene Ciloleucel — BIOLOGICAL
  Given IV
• Biospecimen Collection — PROCEDURE
  Undergo collection of blood and tissue samples
• Computed Tomography — PROCEDURE
  Undergo PET-CT or CT
• Cyclophosphamide — DRUG
  Given IV
• Fludarabine — DRUG
  Given IV
• Lisocabtagene Maraleucel — BIOLOGICAL
  Given IV
• Mosunetuzumab — BIOLOGICAL
  Given IV
• Patient Observation — OTHER
  Undergo observation
• Polatuzumab Vedotin — DRUG
  Given IV
• Positron Emission Tomography — PROCEDURE
  Undergo PET-CT
• Tisagenlecleucel — BIOLOGICAL
  Given IV

Study Details

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 Dates

Start date

Jun 12, 2023

Status verified

Jan 2026

Primary completion

Jun 30, 2030

Completion

Jun 30, 2030

Study Design

Enrollment

396 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• 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.

Primary Outcome Measure

Progression free survival (PFS) [ Time Frame: From date of randomization to date of first observation of progressive disease or death due to any cause, assessed up to 2 years ]

Central Contacts

• Erin Rogers
  210-614-8808
  [email protected]
• Dana Sparks
  210-614-8808
  [email protected]

Locations (87)

Find similar trials in Tucson, AZ

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