NY-ESO-1 TCR Engineered T Cell and HSC After Melphalan Conditioning Regimen in Treating Participants With Recurrent or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Sponsor:
Roswell Park Cancer Institute
Collaborators:
Information provided by (Responsible Party):
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| Tracking Information | |||
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| First Submitted Date ICMJE | September 27, 2018 | ||
| First Posted Date ICMJE | October 1, 2018 | ||
| Last Update Posted Date | October 1, 2018 | ||
| Actual Study Start Date ICMJE | October 1, 2018 | ||
| Estimated Primary Completion Date | October 1, 2019 (Final data collection date for primary outcome measure) | ||
| Current Primary Outcome Measures ICMJE |
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. |
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| Original Primary Outcome Measures ICMJE | Same as current | ||
| Current Secondary Outcome Measures ICMJE |
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| Descriptive Information | |||
| Brief Title ICMJE | NY-ESO-1 TCR Engineered T Cell and HSC After Melphalan Conditioning Regimen in Treating Participants With Recurrent or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer |
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| Official Title ICMJE | 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 |
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| Brief Summary | This phase I trial studies the best dose and side effects of NY-ESO-1 T cell receptor (TCR) engineered T cells and how well they work with NY-ESO-1 TCR engineered hematopoietic stem cells (HSCs) after melphalan conditioning regimen in treating participants with ovarian, fallopian tube, or primary peritoneal cancer that has come back or does not respond to treatment. The melphalan conditioning chemotherapy makes room in the patient's bone marrow for new blood cells and blood-forming cells (stem cells) to grow. Giving NY-ESO-1 TCR T cells and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer. Giving NY-ESO-1 TCR engineered T cells and HSCs after melphalan may work better in treating participants with ovarian, fallopian tube, or primary peritoneal cancer. |
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| Detailed Description | PRIMARY OBJECTIVES: 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, in combination with decitabine that is given prior to the cell infusion (and conditioning regimen) to induce/increase the NY-ESO-1 antigen expression. SECONDARY OBJECTIVES: 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. Participants receive decitabine intravenously (IV) over 1 hour once daily (QD) on days -10 to -6 and 78-82, and melphalan IV over 30 minutes on day -1. Participants 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 on days 3 and 90. Participants also receive aldesleukin subcutaneously (SC) twice daily (BID) on days 4-17 and 91-104. After completion of study treatment, participants are followed up every 6 months for 5 years, then annually for up to 15 years. | ||
| Study Type ICMJE | Interventional | ||
| Study Phase | Phase 1 | ||
| Study Design ICMJE | Allocation: Intervention Model: Single Group Assignment Intervention Model Description: Masking: Interventional Masking Description: Primary Purpose: Treatment |
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| Intervention ICMJE |
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| Recruitment Information | |||
| Recruitment Status ICMJE | Not yet recruiting | ||
| Estimated Enrollment ICMJE |
18 | ||
| Original Estimated Enrollment ICMJE | Same as current | ||
| Estimated Study Completion Date | October 1, 2020 | ||
| Estimated Primary Completion Date | October 1, 2019 (Final data collection date for primary outcome measure) | ||
| Eligibility Criteria ICMJE | Inclusion Criteria: - Must have a diagnosis of platinum-sensitive or platinum-resistant recurrent or refractory epithelial ovarian, primary peritoneal or fallopian tube carcinoma - Received not more than 3 prior lines of chemotherapy - Have been informed of other treatment options - Must be HLA- A*02.1 and HLA-DP*04 positive. Retesting is not required for patients who have previous documented positivity - Have an Eastern Cooperative Oncology group (ECOG) performance status of 0 or 1 - Life expectancy of > 4 months - At least 4 weeks from prior chemotherapy, radiotherapy or immunotherapy, or prior investigational agents - Must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Must have adequate venous access for apheresis (pheresis catheter placement for cell collection is allowed) - Since the study drug may affect pregnancy since it targets proteins present during development, women of childbearing potential are requested to use acceptable methods of birth control for the duration of the study and until persistence of the study drug is no longer detected in the patient by polymerase chain reaction (PCR). This may be a period of several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception. It is recommended that a combination of two methods be used - Leukocytes >= 3 x 10^9/L - Absolute neutrophil count >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal - Creatinine =< upper limit of normal (ULN); if creatinine level > ULN, then creatinine clearance must be > 60 mL/min - Patient must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: - Patients may not be receiving any other investigational agents - Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with prior history of brain metastasis who have undergone local therapy (i.e., metastasectomy and/or radiation) and show no evidence of local recurrence or progression over the past 6 months are eligible - History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study - Prior malignancy (except non melanoma skin cancer) within 3 years - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements - Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin 2, interferon alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to study entry - NOTE: Recent or current use of inhaled steroids is not exclusionary. If subjects are prescribed a brief course of oral corticosteroids, the use should be limited to less than 7 days. Use of steroids before apheresis and immune assessment blood draws should be discouraged as it will affect white blood cell function - Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) as defined below, due to the immunosuppressive effects of chemo-conditioning used and the unknown risks associated with viral replication - Positive serology for HIV - Active hepatitis B infection as determined by test for hepatitis B surface antigen (Ag) - Active hepatitis C. Patients will be screened for HCV antibody. If the HCV antibody is positive, a screening HCV ribonucleic acid (RNA) by any reverse transcriptase (RT) PCR or branched deoxyribonucleic acid (bDNA) assay must be performed at screening by a local laboratory with a Clinical Laboratory Improvement Act (CLIA) certification or its equivalent. Eligibility will be determined based on a negative screening value. The test is not required if documentation of a negative result of a HCV RNA test performed within 60 days prior to screening is provided. - Serology (CMV IgG) positive for active CMV - Received any previous gene therapy using an integrating vector within 6 months - Pregnancy or breast-feeding - Lack of availability of a patient for immunological and clinical follow up assessment - Evidence or history of significant cardiac disease (including MI in the past 6 months, significant cardiac arrhythmia, stage III or IV congestive heart failure [CHF]). Cardiac stress test will be done if clinically indicated. (The specific test to be chosen at the discretion of the principal investigator [PI]) - Patients with pulmonary function test abnormalities as evidenced by a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 70% of predicted for normality will be excluded | ||
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| Ages | 18 Years and older (Adult, Older Adult) | ||
| Accepts Healthy Volunteers | No | ||
| Listed Location Countries ICMJE | United States | ||
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| Administrative Information | Has Data Monitoring Committee | Yes | |
| U.S. FDA-regulated Product |
Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No |
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| IPD Sharing Statement |
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| Responsible Party | ， | ||
| Study Sponsor ICMJE | Roswell Park Cancer Institute | ||
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| Investigators ICMJE |
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| PRS Account | |||
| Verification Date | September 2018 | ||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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