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

Phase 1

Active, not recruiting

• Conditions: High Grade Serous Ovarian Cancer; Primary Peritoneal Cancer; Recurrent; Platinum-resistant; Fallopian Tube Cancer
• Interventions: Biological: Re-stimulated tumor-infiltrating lymphocytes (TILs); Biological: Interleukin-2; Drug: Cyclophosphamide

• Registration Number: NCT01883297
• Lead Sponsor: University Health Network, Toronto

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2013-06-11
• Study First Submitted QC: 2013-06-18
• Study First Posted: 2013-06-21
• Study Start: 2015-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-20
• Last Update Posted: 2024-03-22
• Primary Completion: 2024-06
• Study Completion: 2024-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2	Re-stimulated tumor-infiltrating lymphocytes (TILs)	Cyclophosphamide will be given prior to Re-Stimulated Tumor-Infiltrating Lymphocytes, and interleukin-2.
Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2	Interleukin-2	Cyclophosphamide will be given prior to Re-Stimulated Tumor-Infiltrating Lymphocytes, and interleukin-2.
Re-Stimulated Tumor-Infiltrating Lymphocytes and interleukin-2	Cyclophosphamide	Cyclophosphamide will be given prior to Re-Stimulated Tumor-Infiltrating Lymphocytes, and interleukin-2.

Primary Outcome Measures

Name	Time	Method
Number of occurrences and severity of side effects	Starting at first dose of study treatment up to 10 years	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.

Secondary Outcome Measures

Name	Time	Method
Clinical response to treatment	6 weeks after treatment	Evaluation of the clinical response (clinical tumor regression), which will be monitored and reported according to RECIST v1.1 criteria and Immune-Related Response Criteria.
Number of patients with an immunity and no immunity to the study treatment	From start of the study up to 11 years	Immunological assessments of peripheral blood mononuclear cells, serum and tissue biopsies (if any) will be reported using units appropriate to each particular assay. Results from immunohistochemical evaluations of tissue biopsies will be reported descriptively. Descriptive statistics will be used to summarize immunological findings. Any correlation with clinical response rate will be reported descriptively.

Trial Locations

Locations (1)

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada