A Multi-Center Phase Ib / II Trial of Nivolumab / Ipilimumab-Primed Immunotransplant for Relapsed / Refractory Diffuse Large B Cell Lymphoma Patients

Status
Temporarily Closed
Cancer Type
Lymphoma
Trial Phase
Phase I
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCD ID
NCT03305445
Protocol IDs
17-2164 (primary)
NCI-2018-00677
Study Sponsor
Icahn School of Medicine at Mount Sinai

Summary

This phase Ib / II trial studies the side effects of nivolumab, ipilimumab, and immunotransplant and to see how well they work in treating participants with diffuse large B cell lymphoma that has come back or that isn't responding to treatment. Monoclonal antibodies, such as ipilimumab and nivolumab, may interfere with the ability of cancer cells to grow and spread. Immunotransplant is a treatment used to help the immune system fight diseases such as cancer. T cells are collected from a participant and grown in the laboratory, which increases the number of T cells that are able to kill cancer cells or fight infections. These T cells are then given back to the participant to help the immune system fight disease. Giving ipilimumab and nivolumab with immunotransplant may help treat participants with diffuse large B cell lymphoma.

Objectives

PRIMARY OBJECTIVES:
I. A fixed-dose cohort to evaluate the safety and feasibility of dual checkpoint blocking antibody (DCBA) in patients treated with non-ablative chemotherapy. (phase Ib)
II. Assess the complete response (CR) rate in patients as per the Lugano criteria, determined by positron emission tomography/computed tomography (PET/CT) imaging at 3 months following the 4th dose of DCBA (phase II).

SECONDARY OBJECTIVES:
I. Assess one and two year progression-free survival (PFS), from the time of adoptive T cell transfer (ATCT) (day 0 [D0]) until the first recurrence or progression of disease as per the Lugano criteria, or date of death if the subject dies from any cause before progression is documented (phase II).
II. Assess one and two year overall survival (OS), from the time of ATCT (D0) until recorded date of death (phase II).
III. Assess overall response rate (ORR), defined as complete remission/partial remission/stable disease (CR/PR/SD) as per the Lugano criteria, determined by PET/CT imaging at 3 months following the 4th dose of DCBA (phase II).
IV. Assess delayed CR, defined as CR as per the Lugano criteria, determined at the PET/CT imaging assessments at 6, 9, 12, 18 and 24 months (phase II).
V. Assess side effect profiles, experienced before immunotransplant (after the first 2 doses of DCBA, before chemotherapy), after ATCT, after the 4th dose of DCBA, and during the maintenance phase of DCBA (phase II).
VI. Assess rate of, and time to achieving molecular remission as determined by serum analysis for persistent immunoglobulin variable region heavy chain (IgVH) by polymerase chain reaction (PCR) (phase II).
VII. Assess effect of microbiome on efficacy of immunotransplant, looking at diversity as well as specific microorganisms which have been implicated in the success/failure of checkpoint-inhibitor therapies (phase II).
VIII. Assess enrichment of tumor reactive T cells in circulation by flow cytometry. (Immune monitoring) (phase II).
IX. Provide detailed phenotypic description of immune repertoire (T cell subset focus) per mass cytometry (CyTOF) performed on tumor biopsy as well as peripheral blood mononuclear cells (PBMCs) harvested before initial treatment with DCBA, at time of T cell apheresis following initial two cycles of DCBA, following count recovery from immunotransplant before discharge and 6 weeks following completion of 4th dose of nivolumab/ipilimumab. (Immune monitoring) (phase II).

OUTLINE:
Participants receive standard rituximab on day -54 and -11, ipilimumab intravenously (IV) and nivolumab IV on days -53 and -32, and cyclophosphamide IV and fludarabine IV on days -5 to -3. Participants then undergo immunotransplant (ATCT) IV over 15 minutes on day 0 followed by ipilimumab IV and nivolumab IV on days 1 and 22. Beginning 21 days later, participants then receive nivolumab IV every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 3 months for 12 months, and then again at 18 and 24 months. Additional follow up during years 3-5 is per the discretion of the investigator and standard operation procedures (SOP) of the institution.