Autologous T Cells Expressing Enhanced TCRs Specific for NYESO-1/LAGE in Patients With Ovarian Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Adaptimmune
Sponsor:
Information provided by (Responsible Party):
Adaptimmune
ClinicalTrials.gov Identifier:
NCT01567891
First received: March 16, 2012
Last updated: June 27, 2013
Last verified: June 2013
  Purpose

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/LAGE". 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.


Condition Intervention Phase
Ovarian Cancer
Biological: T cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IIa, Open Label, Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY ESO 1/LAGE-1 in Patients With Recurrent or Treatment Refractory Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Adaptimmune:

Primary Outcome Measures:
  • NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3 [ Time Frame: Month: 9 ] [ Designated as safety issue: Yes ]
    To determine the safety and tolerability of autologous redirected T cell therapy in patients with treatment refractory or resistant Stage III/IV ovarian cancer.


Secondary Outcome Measures:
  • Tumor Measurements [ Time Frame: Month 9 ] [ Designated as safety issue: No ]
    Secondary study objectives are: 1) to determine the effect of the treatment on tumor as determined by irRC and progression free survival, 2) to evaluate the persistence of genetically modified cells in the peripheral blood, and as possible at tumor sites, and 3) to evaluate the phenotype and functionality of genetically modified cells isolated from peripheral blood and, as possible, from tumor sites post infusion.


Estimated Enrollment: 6
Study Start Date: June 2013
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Subjects who are HLA A201 positive and their tumor expresses NY-ESO-1 and/or LAGE positive.
Biological: T cells
Subjects who are HLA A201 positive and their tumor expresses NY-ESO-1 and/or LAGE positive will undergo apheresis, T cell infusion and frequent follow up for 9 months. Subjects will then undergo long term follow up for up to 15 years.

Detailed Description:

This is an open label clinical trial. Patients with the HLA-A201 allele and whose tumor expresses the NY-ESO-1 and/or LAGE-1 tumor antigen will be eligible to receive NY ESO 1c259 T. The trial is conducted entirely with outpatient procedures; however, patients may be hospitalized for the cytoreductive chemotherapy at the discretion of the investigator. Upon enrollment, patients will undergo leukapheresis for T cell collection, and their cells will be genetically engineered and expanded ex vivo. Seven days prior to receiving T-cells patients will undergo a cyclophosphamide conditioning regimen to potentiate the immunotherapy. The cell product will be infused as a split infusion (30% Day 0 and 70% Day 1; typically Monday and Tuesday) to mitigate risks associated with unanticipated infusion reactions. Patients will be followed daily for the first week, weekly until 4 weeks, 8 weeks, and 12 weeks and then at 6 months and 9 months. Patients will undergo disease monitoring by MRI/CT scan (as appropriate for disease) at baseline, day 28, 8 weeks and 12 weeks, and months 6, and 9 or until progression, whichever comes first. Optional tumor biopsies will be taken at baseline, at Day 28, and upon progression, if applicable.

In patients who have progressive disease following initial infusion but whose tumors continue to express the appropriate antigen target, these patients will be eligible for a second infusion with redirected T cells.

At 9 months, the interventional portion of the protocol ends and long term follow-up (LTFU) begins at 1 year, in accordance with FDA regulations. LTFU occurs semiannually for up to 5 years post infusion and then annually thereafter for up to 15 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Measurable disease as defined by RECIST Criteria (V1.1)
  • HLA-A201 and tumor express NY-ESO-1 and/or LAGE or HLA-A101 then the tumor must express MAGE-A3 and/or MAGE-A6 and/or MAGE-B18.
  • Last chemotherapy, radiotherapy or immunotherapy, or prior investigational agents was longer than 4 weeks prior to study entry.
  • Normal organ and bone marrow function (ANC ≥ 1,500/mcL; Platelets ≥ 100,000/mcL; Creatinine ≤ 2.0 mg/dL; AST/ALT ≤ 2.5 x ULN; Total Bilirubin WNL; Leucocytes ≥ 3,000/mcL)
  • Life expectancy of greater than 4 months; ECOG PS of 0 or 1

Exclusion Criteria:

  • Pregnant
  • Active brain metastases
  • Active HIV, Hepatitis B, Hepatitis C infection
  • Received an experimental vaccine within 6 months
  • Received any previous gene therapy using an integrating vector
  • Allergy to Cyclophosphamide, Mesna
  • Prior malignancy within the past 3 years (except non-melanoma skin cancer)
  • Active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
  • Chronic use of the following within 30 days prior to study entry: corticosteroids, hydroxyurea or immunomodulating agents (interleukin-2, interferon-alpha, interferon gamma, granulocyte colony stimulating factors (inhaled steroids OK)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01567891

Contacts
Contact: RPCI Hotline 877-275-7724 askrpci@roswellpark.org

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Kunle Odunsi, MD, PhD    716-845-3497    Kunle.Odunsi@roswellpark.org   
Principal Investigator: Kunle Odunsi, MD, PhD         
Sponsors and Collaborators
Adaptimmune
Investigators
Study Chair: Kunle Odunsi, MD, PhD Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT01567891     History of Changes
Other Study ID Numbers: ADP-0011-001, 230612
Study First Received: March 16, 2012
Last Updated: June 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Adaptimmune:
Ovarian Cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 30, 2014