T-Cell Infusion, Aldesleukin, and Utomilumab in Treating Patients With Recurrent Ovarian Cancer
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|ClinicalTrials.gov Identifier: NCT03318900|
Recruitment Status : Recruiting
First Posted : October 24, 2017
Last Update Posted : March 12, 2020
|Condition or disease||Intervention/treatment||Phase|
|COL6A3 Positive HLA-A*0201 Positive Cells Present PRAME Positive Recurrent Ovarian Carcinoma||Biological: Aldesleukin Drug: CD8-Positive T-Lymphocyte Drug: Cyclophosphamide Procedure: Leukapheresis Biological: Utomilumab||Phase 1|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||July 16, 2018|
|Estimated Primary Completion Date :||July 31, 2020|
|Estimated Study Completion Date :||July 31, 2020|
Experimental: Treatment (T-cell infusion, aldesleukin, utomilumab)
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.
Drug: CD8-Positive T-Lymphocyte
- Dose Limiting Toxicity Summary associated with Utomilumab Dose Escalation [ Time Frame: Up to 6-8 weeks ]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).
- Duration of in vivo persistence [ Time Frame: Up to 6 months after the T cell infusion ]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.
- Maximum Tolerated Dose (MTD) of T Cells [ Time Frame: 6 weeks ]Bayesian optimal interval (BOIN) design is used for dose escalation and finding the maximum tolerated dose (MTD).
- Maximum Tolerated Dose (MTD) of T cells + Utomilumab [ Time Frame: 8 weeks ]Bayesian optimal interval (BOIN) design is used for dose escalation and finding the maximum tolerated dose (MTD).
- Best overall response rate (BORR) [ Time Frame: 12 weeks up to 1 year ]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.
- Progression free survival (PFS) [ Time Frame: 6 months after the T cell infusion ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03318900
|Contact: Ljiljana Milojevic||713-792-8578||Lmilojev@mdanderson.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Amir A. Jazaeri 713-792-2921 firstname.lastname@example.org|
|Principal Investigator: Amir A. Jazaeri|
|Principal Investigator:||Amir A Jazaeri||M.D. Anderson Cancer Center|