"Re-Stimulated" Tumor-Infiltrating Lymphocytes And Low-Dose Interleukin-2 Therapy in Patients With Platinum Resistant High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by University Health Network, Toronto
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01883297
First received: June 11, 2013
Last updated: March 27, 2015
Last verified: March 2015
  Purpose

This is a phase I clinical study for patients with platinum resistant (does not respond to platinum-based chemotherapy) high grade serous ovarian, fallopian tube, or primary peritoneal cancer. Prior to the main treatment, patients will receive cyclophosphamide by vein. Patients will then receive an infusion (given by vein) of autologous tumor-infiltrating lymphocytes (TILs) which will first be taken from the patient, then be stimulated with certain substances called autologous dendritic cells (DCs) and OKT3 (anti-CD3 antibody), and then given back to the patient as an infusion. This is believed to make the TILs work better. TILs are a type of white blood cells that recognizes tumor cells and enter them which causes the tumor cells to break down. After infusion of TILs, low-dose interleukin-2 (IL-2) therapy will be given.


Condition Intervention Phase
Recurrent, Platinum Resistant High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Biological: Re-stimulated tumor-infiltrating lymphocytes (TILs)
Biological: Interleukin-2
Drug: Cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Evaluating the Feasibility and Safety of Infusion of "Re-Stimulated" Autologous Tumor-Infiltrating Lymphocytes (TILs) Followed by Low-Dose Interleukin-2 Therapy in Patients With Platinum Resistant High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Number occurrences and severity of side effects [ Time Frame: Starting at first dose of study treatment up to 10 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical response to treatment [ Time Frame: 6 weeks after treatment ] [ Designated as safety issue: No ]
  • Number of patients with an immunity and no immunity to the study treatment [ Time Frame: From start of the study up to 10 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 9
Study Start Date: January 2015
Estimated Study Completion Date: December 2023
Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2
Cyclophosphamide will be given prior to Re-Stimulated Tumor-Infiltrating Lymphocytes, and interleukin-2.
Biological: Re-stimulated tumor-infiltrating lymphocytes (TILs)
Intravenous infusions: Dose level 1 (3 patients): 3x10^7 TILs (with maximum 3x10^6 autologous dendritic cells); Dose level 2 (3 patients): 1x10^8 TILs (with maximum 1x10^7 autologous dendritic cells); Dose level 3 (3 patients): 3x10^8 TILs (with maximum 3x10^7 autologous dendritic cells)
Biological: Interleukin-2
Subcutaneous injections of IL-2 x 4 days during the first week and x 5 days the second week with 2 days of rest in between each week of dosing
Other Name: Aldesleukin, Proleukin, Recombinant Human Interleukin 2
Drug: Cyclophosphamide
Intravenous infusion: 30 mg/kg/day for 2 days (Day -3 and -2 prior to infusion of TILs)
Other Name: Procytox

  Eligibility

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

Inclusion Criteria (Eligibility for TIL Evaluation):

  • Platinum resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer
  • Suitable tumor for collection
  • If tumor is suitable for collection, patient must be suitable for surgery
  • Patient must be 18 years of age or older
  • Performance status of ECOG 0 or 1
  • Life expectancy > 5 months from date of consent of TIL evaluation

Inclusion Criteria (Eligibility for Treatment):

  • Signed and dated the informed consent
  • Recurrent high grade serous ovarian, fallopian tube, primary peritoneal cancer
  • Measurable disease by RECIST 1.1.
  • No brain metastases. Note if brain metastases are present, these lesions must undergo definitive treatment with surgery and/or radiation at least 30 days prior to the first dose of lymphodepleting chemotherapy
  • Performance status of ECOG 0 or 1
  • Life expectancy > 3 months from the date of consent for TILs treatment
  • TILs are suitable for use as determined by laboratory
  • More than 30 days since any prior systemic therapy at the time of the cell infusion. All subjects' toxicities must have recovered to a CTCAE grade 1 or less; however, patients with residual CTCAE grade 2 neuropathy from previous carboplatin/taxol treatment will not be excluded. Subjects may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to CTCAE grade 1 or less or as specified in the inclusion criteria listed above.
  • Adequate organ function
  • Women of child-bearing potential must have a negative pregnancy test. Patients must be willing to practice birth control during treatment and for 6 months post completion of IL-2 treatment

Exclusion Criteria:

  • Requiring systemic steroid therapy within 4 wks before TIL infusion. Use of intranasal and inhaled corticosteroids, or systemic corticosteroids at physiologic doses are allowed. Oral steroid use as premedication to prevent allergic reactions to radiologic contrast is allowed.
  • HIV positive
  • With active hepatitis B or hepatitis C, syphilis, or HTLV
  • The number of prior lines of chemotherapy is not limited. However, if the subject has had ≥3 lines of prior chemotherapy for platinum refractory or platinum resistant disease, documentation of a response to one of these lines is required.
  • Must not have any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, uncontrolled psychiatric disorders, or other conditions that may affect following study procedures.
  • Have no active underlying cardiac illnesses defined by positive stress test, LVEF<40% or ongoing life-threatening arrhythmias
  • abnormal pulmonary function test as evidenced by a FEV1 < 60% predicted.
  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: NCT01883297

Locations
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Marcus Butler, M.D.    416-946-4628    marcus.butler@uhn.ca   
Principal Investigator: Marcus Butler, M.D.         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Marcus Butler, M.D. Princess Margaret Cancer Centre
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01883297     History of Changes
Other Study ID Numbers: TILs-001-DC
Study First Received: June 11, 2013
Last Updated: March 27, 2015
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by University Health Network, Toronto:
Measurable
Recurrent
Platinum resistant
Tumor-Infiltrating Lymphocytes
Low-Dose Interleukin-2
Autologous dendritic cells
Anti-CD3 monoclonal antibody
High grade serous ovarian, fallopian tube, or primary peritoneal cancer
Cyclophosphamide

Additional relevant MeSH terms:
Peritoneal Neoplasms
Abdominal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Neoplasms
Neoplasms by Site
Peritoneal Diseases
Aldesleukin
Cyclophosphamide
Interleukin-2
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Central Nervous System Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015