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

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSWOG Cancer Research Network

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Axicabtagene Ciloleucel

    Biological/Vaccine

    Given IV

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood and tissue samples

  • Computed Tomography

    Procedure/Surgery

    Undergo PET-CT or CT

  • Cyclophosphamide

    Drug

    Given IV

  • Fludarabine

    Drug

    Given IV

  • Lisocabtagene Maraleucel

    Biological/Vaccine

    Given IV

  • Mosunetuzumab

    Biological/Vaccine

    Given IV

  • Patient Observation

    Other intervention

    Undergo observation

  • Polatuzumab Vedotin

    Drug

    Given IV

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET-CT

  • Tisagenlecleucel

    Biological/Vaccine

    Given IV

Treatment groups

396 Participants
are divided into 5 treatment groups
Group A: Step I (lymphodepleting chemotherapy)Experimental treatment 6 interventions
Group B: Step II Arm I (mosunetuzumab)Experimental treatment 4 interventions
Group C: Step II Arm II (polatuzumab vedotin)Experimental treatment 4 interventions
Group D: Step II Arm III (polatuzumab vedotin, mosunetuzumab)Experimental treatment 5 interventions
Group E: Step II Arm IV (observation)Active comparator 4 interventions

Trial outcomes

Primary outcomes

1

Progression free survival (PFS)

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.

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

Secondary outcomes

1

Overall survival (OS)

Will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.

Time frame
From date of randomization to date of death due to any cause, assessed up to 2 years
2

Complete remission (CR) conversion rate

The complete remission conversion rate up to one year after randomization will be calculated and compared using Cochran-Mantel-Haenszel test with a two-sided alpha of .05.

Time frame
Up to 1 year after randomization
3

Incidence of adverse events

Time frame
Up to 2 years
4

Association between total metabolic tumor volume (TMTV), standardized uptake value (SUV) max, and sum product (SPD) of diameters

The association between TMTV, SUV max, and SPD by PET-CT at first imaging response as a continuous variable will be assessed using a univariate logistic regression with a two-sided alpha of .05, respectively.

Time frame
Up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

SWOG Cancer Research Network

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Genentech, Inc.

Collaborator