"Re-Stimulated" TILs and IL-2 Therapy for Platinum Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT01883297 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: TILs-001-DC
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I clinical study for patients with platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer, and the response to a combination of cyclophosphamide, autologous tumor-infiltrating lymphocytes (TILs), autologous dendritic cells (DCs), and OKT3 (anti-CD3 antibody), along with low-dose interleukin-2 (IL-2) therapy.

Conditions

Recurrent; Platinum-resistant; High Grade Serous Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer

Keywords

Measurable; Recurrent; Platinum resistant; Tumor-Infiltrating Lymphocytes; Low-Dose Interleukin-2; Autologous dendritic cells; Anti-CD3 monoclonal antibody; High grade serous ovarian cancer; Fallopian tube cancer; Primary peritoneal cancer; Cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Number of occurrences and severity of side effects

  Toxicities will be monitored on an ongoing basis by the investigators. Toxic effects will be categorized using the CTCAE v4.0 and will be reported using summary statistics. The highest toxicity for each patient in each category or subcategory will be described. Both events related and unrelated to treatment will be captured. The total number of episodes for each event reported, the severity and attribution to study therapy of each episode reported will also be displayed.

  Starting at first dose of study treatment up to 10 years

Secondary Outcomes (2)

• Clinical response to treatment

  6 weeks after treatment

• Number of patients with an immunity and no immunity to the study treatment

  From start of the study up to 11 years

Study Arms (1)

Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2

EXPERIMENTAL

Cyclophosphamide will be given prior to Re-Stimulated Tumor-Infiltrating Lymphocytes, and interleukin-2.

Biological: Re-stimulated tumor-infiltrating lymphocytes (TILs); Biological: Interleukin-2; Drug: Cyclophosphamide

Interventions

Re-stimulated tumor-infiltrating lymphocytes (TILs) BIOLOGICAL

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)

Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2

Interleukin-2 BIOLOGICAL

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

Also known as: Aldesleukin, Proleukin, Recombinant Human Interleukin 2

Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2

Cyclophosphamide DRUG

Intravenous infusion: 30 mg/kg/day for 2 days (Day -3 and -2 prior to infusion of TILs)

Also known as: Procytox

Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2

Eligibility Criteria

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

You may qualify if:

• Platinum resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
• 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.
• If tumor harvest is required, subject must be a suitable surgical candidate in the opinion of the operating surgeon.
• Patient age: ≥ 18 years.
• Clinical performance status of ECOG 0 or 1.
• Life expectancy \> 5 months from the date of consent for TIL evaluation.
• Ability to understand and has signed the Pre-Screening Consent Form.
• 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)
• Confirmation that the Translational Immunotherapy Lab is able to process the specimen
• 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).
• 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.
• Recurrent platinum resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer, with evidence of disease progression from previous line of treatment.
• Measurable disease by RECIST 1.1.
• 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.
• Clinical performance status of ECOG 0 or 1.

You may not qualify if:

• 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.
• Subjects cannot be HIV positive.
• Subjects cannot have active hepatitis B or hepatitis C, syphilis, or Human T-Cell Lymphotropic Virus (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. Response can be defined by RECIST 1.1 or CA125 as defined by the modified GCIG criteria (See Section 11).
• 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.
• 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).
• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Recurrence; Fallopian Tube Neoplasms

Interventions

Interleukin-2; aldesleukin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Marcus Butler, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 21, 2013
• Study Start: January 1, 2015
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: September 5, 2024

Record last verified: 2024-08

Locations

CA (1)