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Serine

Patients undergo leukapheresis. Patients then receive cyclophosphamide IV on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin SC every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity.

CD8-Positive T-Lymphocyte

Leukapheresis

Utomilumab

Amir A Jazaeri

This phase I/Ib trial studies the side effects and best dose of utomilumab and how well it works with CD8-positive T-lymphocyte (T-cell infusion) and aldesleukin in treating patients with ovarian cancer that has come back. Aldesleukin may stimulate white blood cells to kill ovarian cancer cells. Giving white blood cells (T-cells) that have been activated by a vaccine with aldesleukin may kill more tumor cells. Immunotherapy with utomilumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving T-cell infusion with aldesleukin and utomilumab may work better in treating patients with ovarian cancer.

PRIMARY OBJECTIVES:

I. Assess the safety and toxicity of adoptively transferred central memory-type CTL targeting ovarian cancer antigens administered alone, and in combination with, utomilumab, an agonistic anti-CD137 antibody, in patients with platinum-resistant ovarian cancer.

II. Evaluate the functional and numeric in vivo persistence of adoptively transferred central memory-type CTL with and without utomilumab.

SECONDARY OBJECTIVES:

I. Evaluate the anti tumor effect of adoptively transferred central memory-type CTL targeting ovarian cancer antigens as measured by best overall response rate (BORR) and progression free survival (PFS).

OUTLINE: This is a dose escalation study of utomilumab.

Patients undergo leukapheresis. Patients then receive cyclophosphamide intravenously (IV) on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin subcutaneously (SC) every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at days 3, 7, 14, 22, 28, 35, 43, 49, 56, 64, 70, 77, 84, 112, and 140.

T-Cell Infusion, Aldesleukin, and Utomilumab in Treating Patients With Recurrent Ovarian Cancer

Phase I/Ib Study of Adoptive Cellular Therapy Using Autologous IL-21-Primed CD8+ Tumor Antigen-Specific T Cells in Combination With Utomilumab (PF-05082566) in Patients With Platinum Resistant Ovarian Cancer

Safety and toxicity of adoptively transferred central memory-type CTL targeting ovarian cancer antigens administered alone, and in combination with, an Utomilumab, an agonistic anti-CD137 antibody, in patients with platinum resistant ovarian cancer reported at each dose level. Safety and toxicity will be assessed using the latest version of Common Terminology Criteria for Adverse Events (CTCAE).

To evaluate the functional and numeric in vivo persistence of adoptively transferred central memory-type CTL with and without Utomilumab, duration of in vivo persistence defined as the time between T cell infusion and last time point at which the transferred T cell DNA signature is detectable in peripheral blood. Transferred antigen-specific T cells will be tracked by tetramer analysis as well as by TCR tracking (Immunoseq assay, Adaptive Biotech), both assays, have been established in lab as reliable measures of T cell persistence.

Bayesian optimal interval (BOIN) design is used for dose escalation and finding the maximum tolerated dose (MTD).

BORR is defined as the total number of participants who's BOR is complete response (CR) or partial response (PR), divided by the total number of participants. Radiographic imaging and clinical assessment of residual disease will be compared with pre-infusion baseline assessment according to modified RECIST 1.1 for response: complete response (CR) defined as total regression of all tumor, a partial response (PR) as 30% or greater decrease in sum of longest diameter of target lesions and progressive disease (PD) as 20% increase in sum of longest diameter of target lesions (modified world health organization criteria or mWHO). Assessment at 6 and 12 weeks following T cell infusion and then every 8 weeks (+/- 1 week) until disease progression or intervening therapy. The overall response rate (OR) will be after 1 cycle (12) weeks.

PFS is defined as the time between T cell infusion date and the date of progression or death. A participant who dies without reported prior progression will be considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS will be censored on the date of last tumor assessment. For participants who have PD prior to Week 12 and a subsequent assessment of SD, PR or CR, the date of PD following response (where available) will be used in the analysis of PFS; otherwise these participants will be censored on the date of their last tumor assessment. PFS is estimated for each arm using the Kaplan-Meier product limit method.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for col6a3 positive