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"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

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ClinicalTrials.gov Identifier: NCT01883297
Recruitment Status : Recruiting
First Posted : June 21, 2013
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE June 11, 2013
First Posted Date  ICMJE June 21, 2013
Last Update Posted Date June 12, 2018
Study Start Date  ICMJE January 2015
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2013)
Number occurrences and severity of side effects [ Time Frame: Starting at first dose of study treatment up to 10 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01883297 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2016)
  • Clinical response to treatment [ Time Frame: 6 weeks after treatment ]
  • Number of patients with an immunity and no immunity to the study treatment [ Time Frame: From start of the study up to 11 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2013)
  • Clinical response to treatment [ Time Frame: 6 weeks after treatment ]
  • Number of patients with an immunity and no immunity to the study treatment [ Time Frame: From start of the study up to 10 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE "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
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent, Platinum Resistant High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Intervention  ICMJE
  • 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 3x10^8 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
Study Arms  ICMJE Experimental: Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2
Cyclophosphamide will be given prior to Re-Stimulated Tumor-Infiltrating Lymphocytes, and interleukin-2.
Interventions:
  • Biological: Re-stimulated tumor-infiltrating lymphocytes (TILs)
  • Biological: Interleukin-2
  • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 18, 2013)
9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria (Eligibility for TIL Evaluation):

  1. Platinum resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
  2. Tumor is suitable for harvest (i.e., lesion to be harvested for TIL evaluation has a total volume of ≥1cm3) or patient has previously undergone tumor harvest under other REB approved studies involving clinical evaluation of TILs.
  3. If tumor harvest is required, subject must be a suitable surgical candidate in the opinion of the operating surgeon.
  4. Patient age: ≥ 18 years.
  5. Clinical performance status of ECOG 0 or 1.
  6. Life expectancy > 5 months from the date of consent for TIL evaluation.
  7. Ability to understand and has signed the Pre-Screening Consent Form.
  8. Patients are willing to be tested for transmissible diseases (active Hepatitis B (HBV) or Hepatitis C (HCV), human immunodeficiency virus (HIV), Human T-Cell Lymphotropic Virus (HTLV), Herpes Simplex Virus (HSV), Cytomegalovirus (CMV), Syphilis (with West Nile Virus only tested between May 1st and November 30th)
  9. Confirmation that the Translational Immunotherapy Lab is able to process the specimen
  10. If there is a history of allergy to penicillin, gentamycin, streptomycin, or anti-fungals, the ability to generate TILs should first be confirmed with the cell manufacturing lab (i.e., Translational Immunotherapy Laboratory).

Inclusion Criteria (Eligibility for Treatment):

  1. Prior to the performance of any study-specific procedure, the subject has signed and dated the informed consent form, approved by a Research Ethics Board (REB), after the nature of the study has been explained and the subject has had the opportunity to ask questions.
  2. Recurrent platinum resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer, with evidence of disease progression from previous line of treatment.
  3. Measurable disease by RECIST 1.1.
  4. Subjects should have 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. If in the opinion of the PI or his designee the lesion(s) no longer represents active disease, the subject will be considered eligible.
  5. Clinical performance status of ECOG 0 or 1.
  6. Life expectancy > 3 months from the date of consent for TIL treatment.
  7. Laboratory analyses of tumor-infiltrating lymphocytes (TILs) from the subject must demonstrate that the TILs are suitable for use in protocol treatment (performed by the Translational Immunotherapy Laboratory, Princess Margaret Cancer Centre)
  8. More than 30 days has elapsed 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.
  9. Adequate organ function as defined by the following criteria:

    1. Serum ALT ≤ 2.5 x upper limit of normal (ULN) (for patients with liver metastases, serum ALT ≤ 3 x ULN;
    2. Serum AST ≤ 2.5 x upper limit of normal (ULN) (for patients with liver metastases, serum AST ≤ 3 x ULN;
    3. Total serum bilirubin ≤ 2xULN (patients with Gilbert's Syndrome - direct serum bilirubin ≤ 2 x ULN);
    4. Absolute neutrophil count (ANC) ≥ 1.5x109/L;
    5. Platelets ≥100x109/L;
    6. Hemoglobin ≥ 90 g/L for female;
    7. Alkaline phosphatase ≤ 2 x ULN;
    8. Serum creatinine within normal institutional limits OR serum creatinine clearance ≥ 60 mL/min/1.73m2 for patients with creatinine levels above institutional normal;
    9. Serum lipase≤ 1.5 x ULN;
    10. Serum amylase ≤ 1.5 x ULN
  10. Women of child-bearing potential must have a negative pregnancy test. Acceptable birth control failure rate of less than or equal to 1% when used consistently and correctly such as implants, injectables, combined oral contraceptives, double barrier, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner. Subjects are considered to be not of child bearing potential if they are considered to be post-menopausal or surgically sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy. Women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, ovarian suppression or any other reversible reason.

Exclusion Criteria:

  1. Subjects with ongoing or prior use systemic steroid therapy within 4 weeks before the TILs infusion will be excluded. Use of topical, 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.
  2. Subjects cannot be HIV positive.
  3. Subjects cannot have active hepatitis B or hepatitis C, syphilis, or Human T-Cell Lymphotropic Virus (HTLV).
  4. 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. Response can be defined by RECIST 1.1 or CA125 as defined by the modified GCIG criteria (See Section 11).
  5. The subject cannot 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 compliance with the trial.
  6. The subject must have no active underlying cardiac illnesses defined by positive stress test, LVEF<40% or ongoing life-threatening arrhythmias (i.e., for patients older than 60 years of age or otherwise clinically indicated).
  7. Subjects who have a prolonged history of cigarette smoking or symptoms of respiratory dysfunction will be excluded if they have an abnormal pulmonary function test as evidenced by a FEV1 < 60% predicted.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01883297
Other Study ID Numbers  ICMJE TILs-001-DC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marcus Butler, M.D. Princess Margaret Cancer Centre
PRS Account University Health Network, Toronto
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP