Genetically Engineered Cells (NY-ESO-1 TCR Engineered T Cells and HSCs) After Melphalan Conditioning Regimen in Treating Patients With Recurrent or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03691376|
Recruitment Status : Recruiting
First Posted : October 1, 2018
Last Update Posted : May 28, 2020
|Condition or disease||Intervention/treatment||Phase|
|Platinum-Resistant Fallopian Tube Carcinoma Platinum-Resistant Ovarian Carcinoma Platinum-Resistant Primary Peritoneal Carcinoma Platinum-Sensitive Fallopian Tube Carcinoma Platinum-Sensitive Ovarian Carcinoma Platinum-Sensitive Primary Peritoneal Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Refractory Fallopian Tube Carcinoma Refractory Ovarian Carcinoma Refractory Primary Peritoneal Carcinoma||Biological: Aldesleukin Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes Other: Cellular Therapy Drug: Melphalan||Phase 1|
I. To assess the safety and feasibility of intravenous infusion of autologous peripheral blood mononuclear cells (PBMC) and CD34+ peripheral blood stem cells (PBSC) that have been genetically modified ex vivo to express NY-ESO-1 TCR, following a myeloablative conditioning regimen.
Ia. Assessment of toxicities using Common Toxicity Criteria (CTC) and definition of a maximum tolerated dose (MTD).
I. TCR engineered hematopoietic stem cell (HSC) engraftment. II. Functional assays for TCR transgenic cells. III. Progression-free survival (PFS) (compare with the duration of the PFS in the last treatment regimen).
IV. Durable tumor response in at least 30% of the patients defined as immune-related complete response (irCR) or immune-related partial response (irPR) by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria at 6 months.
V. Long-term persistence of TCR transgenic cells (regardless of cell origin) as evidenced by > 5% of CD3 lymphocytes being NY-ESO-1 specific by major histocompatibility complex (MHC) tetramer assay at 3 and 6 months.
VI. Discrimination of TCR transgenic cells resulting from retrovirally-transduced mature lymphocytes and lentivirally-transduced HSCs and their phenotyping.
VII. Long term monitoring for replication competent retrovirus and lentivirus. VIII. Analysis of viral insertion sites in long term persisting NY-ESO-1 TCR clones: absence of a clonal expansion of TCR transgenic cells with a particular transgene insertion site (defined as a clone comprising > 20% of all PBSC-derived gene-marked cells).
IX. Gut microbiota pre and post treatment to evaluate the role of microbiota on the therapeutic efficacy of the proposed therapy.
OUTLINE: This is a dose-escalation study of autologous NY-ESO-1-specific CD8-positive T lymphocytes.
Patients receive melphalan intravenously (IV) over 30 minutes on day -1. Patients then receive autologous NY-ESO-1 CD4-TCR CD34+ HSC IV on day 0 and autologous NY-ESO-1-specific CD8-positive T lymphocytes IV between days 7 and 21. Patients also receive aldesleukin subcutaneously (SC) twice daily (BID) for 14 days on the following day after the T cell infusion (between days 8 and 22).
After completion of study treatment, patients are followed up every 6 months for 5 years, then annually for up to 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I, Open Label Study Evaluating the Safety and Efficacy of Adoptive Transfer of Autologous NY-ESO-1 CD8-TCR Engineered T Cells and NY-ESO-1 CD4-TCR Engineered Hematopoietic Stem Cells (HSC) After a Myeloablative Conditioning Regimen, With Administration of IL-2 in Patients With Recurrent or Treatment Refractory Ovarian, Fallopian Tube or Primary Peritoneal Cancer|
|Actual Study Start Date :||January 24, 2019|
|Estimated Primary Completion Date :||October 1, 2020|
|Estimated Study Completion Date :||October 1, 2021|
Experimental: Treatment (autologous NY-ESO-1 engineered T and HSC)
Patients receive melphalan IV over 30 minutes on day -1. Patients then receive autologous NY-ESO-1 CD4-TCR CD34+ HSC IV on day 0 and autologous NY-ESO-1-specific CD8-positive T lymphocytes IV between days 7 and 21. Patients also receive aldesleukin SC BID for 14 days on the following day after the T cell infusion (between days 8 and 22).
Biological: Autologous NY-ESO-1-specific CD8-positive T Lymphocytes
Other: Cellular Therapy
Given autologous NY-ESO-1 CD4-TCR CD34+ HSC IV
Other Name: Cell Therapy
- Incidence of adverse events [ Time Frame: Up to 9 months post infusion ]The frequency of toxicities will be tabulated by grade across all dose levels and cycles.
- Maximum tolerated dose (MTD) [ Time Frame: Up to 9 months post-infusion ]Dose limiting toxicities will be used in the estimation of the MTD and the accompanying of the dose escalation decisions. The frequency of toxicities will also be tabulated for the dose estimated to be the MTD.
- Change in Immunological parameters associated with T cell persistence [ Time Frame: Baseline up to 15 years ]
- Tumor response rates to treatment [ Time Frame: Up to 15 years ]Based on the immune-related Response Evaluation Criteria in Solid Tumors criteria.
- Progression-free survival [ Time Frame: From start of the treatment until the first occurrence of confirmed progression, assessed up to 15 years ]Will calculate the median progression free survival and the corresponding 95% confidence interval.
- Overall survival [ Time Frame: From start of the treatment until death, assessed up to 15 years ]
- Duration of response [ Time Frame: Up to 15 years ]
- Appearance of target antigen/major histocompatibility complex loss variants upon disease recurrence [ Time Frame: Up to 15 years ]NY-ESO-1 expression will be evaluated by quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) and/or immunohistochemistry. HLA-A*0201 and -DP*04 expression on samples will be evaluated by immunohistochemistry.
- Assessment of bioactivity [ Time Frame: Baseline up to 15 years ]measure pre and post treatment percentage of selective migration into the tumor sites
- Assessment of Immunological parameters associated with functionality [ Time Frame: Baseline up to 15 years ]
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): NCT03691376
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Kunle Odunsi 716-845-8376 firstname.lastname@example.org|
|Principal Investigator: Kunle Odunsi|
|Principal Investigator:||Kunle Odunsi||Roswell Park Cancer Institute|