CT Antigen TCR-redirected T Cells for Ovarian Cancer.

NCT01567891 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: ADP-0011-001230612
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

Brief Summary

This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. These new T cells are called "engineered T cells" because the new gene is causing them to become directed toward the ovarian cancer cells rather than their usual targets. These are also called "gene-modified T cells". For subjects who have the HLA A2 tissue-type marker, the T cells would be engineered to recognize a substance called "NY-ESO-1". After putting this new gene in T cells (a procedure called "gene therapy") the investigators will grow the cells in the laboratory and give these cells back to subjects.

Conditions

Ovarian Cancer

Keywords

Ovarian Cancer; Cell Therapy; T Cell Therapy; NY-ESO-1; Immuno-oncology; Metastatic; Previously treated; T Cell Receptor

Outcome Measures

Primary Outcomes (1)

• Adverse Events Related to Study Treatment

  Number of Participants with Adverse Events related to study treatment

  Up to 12 months

Secondary Outcomes (4)

• Tumor Response

  Change from baseline, every 4 weeks until month 3 and then every 3 month until disease progression

• Peak Persistence of Modified T-cells in the Peripheral Blood

  Days: 1, 2-4, weeks 1 to 4, Week 8, 12 and Month 6, then every 3 months thereafter until progression then during LTFU

• Determine Functional Properties and Phenotype of Modified T-cells From Peripheral Blood.

  Weeks 4 and 8 post T-cell infusion

• Correlate NY-ESO-1 Expression in Tumor Tissue Before Treatment With Archival Tumor Tissue to Assess Impact of Therapy on Expression of NY-ESO-1 Protein

  Screening and at Baseline

Study Arms (1)

Cohort 1

EXPERIMENTAL

This is an open label clinical trial. Patients with the HLA-A201, HLA-A205, and/or HLA-A206 allele and whose tumor expresses the NY-ESO-1 tumor antigen will be eligible to receive NYESO-1c259 T cells.

Biological: NYESO-1c259 T cells

Interventions

NYESO-1c259 T cells BIOLOGICAL

Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells. Patients will receive at least 1x10⁹ transduced cells, however the target dose for this protocol is for patients to receive 5x10⁹ transduced cells with a maximum possible dose of 6x10⁹ administered as a single intravenous (IV) infusion.

Cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a diagnosis of recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum resistant disease and/or have received ≥ 2 lines of chemotherapy
• Age ≥ 18 years of age
• No significant immunodeficiency
• Have been informed of other treatment options
• Must be HLA A\*0201, HLA-A\*0205, and/or HLA-A\*0206 positive by high resolution testing.
• Patient's tumor must be positive by histological assay for NY-ESO-1ᶜ²⁵⁹T, according to the screening algorithm as described in Section 3.3.1. Positive expression is defined as ≥ 50% of cells that are 2+ and/or 3+ by immunohistochemistry
• ECOG performance status of 0 or 1
• Life expectancy of \> 4 months
• Prior therapies:
• prior immunotherapy, or prior investigational agents should be washed out 4 weeks before apheresis and must be completed 4 weeks prior to pre-infusion lymphodepletive chemotherapy.
• monoclonal antibody therapy must be completed at least 6 weeks prior to pre-infusion lymphodepletive chemotherapy
• All previous cytotoxic chemotherapy, monoclonal antibody therapy, immune therapy should be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
• Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy
• Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week before apheresis and must be completed at least 1 week prior to pre-infusion lymphodepletive chemotherapy.
• Any grade 3 or 4 -hematologic toxicity of previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion lymphodepletive chemotherapy.

You may not qualify if:

• Currently receiving any other investigational agents
• Patients with active brain metastases. Patients with prior history of brain metastasis who have undergone local therapy (i.e. metastatectomy 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 cyclophosphamide or other agents used in the study
• Prior malignancy (except non-melanoma skin cancer) within 18 months of study entry NOTE: Patients must be in complete remission from prior malignancy in order to be eligible to enter the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Active infection with HIV, HBV or HCV
• Receipt of an experimental vaccine within 2 months or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months, or has received any previous gene therapy using an integrating vector
• History of severe autoimmune disease requiring steroids or other immunosuppressive treatments
• Lack of availability of a patient for immunological and clinical follow-up assessment
• Evidence or history of significant cardiac disease

Sponsors & Collaborators

• Adaptimmune: lead

Study Sites (5)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trials Management
• Organization: Adaptimmune

clinicaltrials@adaptimmune.com

215-825-9302

Study Officials

• Kunle Odunsi, MD, PhD

  Roswell Park Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2012
• First Posted: March 30, 2012
• Study Start: July 9, 2013
• Primary Completion: June 6, 2017
• Study Completion: June 6, 2017
• Last Updated: June 27, 2019
• Results First Posted: January 3, 2019

Record last verified: 2018-12

Locations

US (5)