Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as KTE C19, KTE-C19 CAR, Yescarta
Axicabtagene Ciloleucel · 1 trial · 7 indications
Will compare PFS 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 (day +30 positron emission tomography \[PET\]/computed tomography \[CT\] scan) after commercial CD19 chimeric antigen receptor (CAR) T-cell therapy who are randomized to receive each consolidation therapy versus those that receive no consolidation therapy (i.e. control). Specifically, will compare the PFS of 1) mosunetuzumab consolidation to no consolidation, 2) polatuzumab vedotin consolidation to no consolidation, 3) mosunetuzumab + polatuzumab vedotin to no consolidation. Will analyze results by arm rather than assuming no-interactions in some factorial analyses. Will follow multi-step hypothesis testing procedure of Freidlin and Korn to compare the arms within this randomized Phase II study. Each of the primary comparisons has 81% power using a stratified logrank test at one-sided alpha of 0.05.
| Arm | Type | Description |
|---|---|---|
| Step I (lymphodepleting chemotherapy) | EXPERIMENTAL | 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. |
| Step II Arm I (mosunetuzumab) | EXPERIMENTAL | 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. |
| Step II Arm II (polatuzumab vedotin) | EXPERIMENTAL | 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. |
| Step II Arm III (polatuzumab vedotin, mosunetuzumab) | EXPERIMENTAL | 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. |
| Step II Arm IV (observation) | ACTIVE_COMPARATOR | 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. |
| Name | Type | Description |
|---|---|---|
| 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 |
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 transfo...