Adoptive Transfer Of Autologous Tumor-Infiltrating Lymphocytes in Solid Tumors

NCT03992326 | Terminated Phase 1 DMC

• 1 other identifier: CHUV-DO-0012-SolTIL_2018
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Single center, single arm phase Ib trial to test the feasibility and safety of Tumor- Infiltrating Lymphocyte-Adoptive Cell Therapy (TIL-ACT) combined with low-dose irradiation in patients with advanced or metastatic solid tumors. The trial is based on lymphodepleting chemotherapy followed by low dose irradiation (LDI), and then ACT utilizing ex vivo expanded TILs in combination with high dose IL-2 (optional, depending on patient's tolerance). LDI will be administered once to metastatic lesions using tomotherapy.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (3)

• Feasibility of TIL-ACT in combination with LDI - successful Rapid Expansion Protocol (REP): Number of patients for whom TIL cultures

  Number of patients for whom TIL cultures after REP achieve the required cell number and release criteria to start TIL-ACT infusion.

  Evaluated for each patient at day 0. After day 0 of the last patient, the number of patients with successful TIL-ACT infusion will be calculated.

• Feasibility of TIL-ACT in combination with LDI - successful infusion: Number of patients receiving a complete TIL-ACT infusion

  Number of patients receiving a complete TIL-ACT infusion (planned NMA chemotherapy, planned LDI and at least partial TIL infusion; no minimum IL-2 required)

  Evaluated for each patient at day 0, up to 60 mins after start of TIL-ACT infusion. At day 0 of the last patient, the number of patients with successful TIL-ACT infusion will be calculated.

• Toxicity of TIL-ACT and LDI

  Number of patients with adverse events as assessed by CTCAE version 5.0

  Treatment limiting toxicity (TLT) period: from chemotherapy start until Day30

Secondary Outcomes (4)

• Disease control rate (DCR)

  1, 3, 6, 9, 12 months

• Objective response rate (ORR)

  1, 3, 6, 9, 12 months

• Progression free survival (PFS) for TIL-ACT

  5 years

• Overall survival (OS)

  5 years

Study Arms (1)

TIL-ACT + LDI

EXPERIMENTAL

Non-myeloablative lymphodepleting chemotherapy (cyclophosphamide and fludarabine), Low Dose Irradiation (LDI), Tumor Infiltrating Lymphocyte (TIL)-Adoptive Cell Therapy (ACT), Interleukin-2 (IL-2).

Other: TIL; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Other: Radiotherapy

Interventions

TIL OTHER

Adoptive transfer of Autologous Tumor-Infiltrating Lymphocytes

TIL-ACT + LDI

Cyclophosphamide DRUG

Cyclophosphamide will be administered as an intravenous (IV) infusion for two days.

TIL-ACT + LDI

Fludarabine DRUG

Fludarabine will be administered as an intravenous (IV) infusion for five days.

TIL-ACT + LDI

Interleukin-2 DRUG

After TIL infusion, IL-2 (optional) will be started as a bolus administration every eight hours, for a maximum of eight doses.

TIL-ACT + LDI

Radiotherapy OTHER

Low-dose irradiation (1Gy) will be administered using tomotherapy to up to 20 measurable tumor lesions once before TIL infusion.

TIL-ACT + LDI

Eligibility Criteria

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

You may qualify if:

• Patients with locally advanced (not radically treatable) or metastatic solid tumors with the below cancer types, who progressed after at least one standard therapy for advanced disease, or for whom such therapy was proven to be intolerable, or is considered inappropriate. Prior immunotherapy is allowed.
• Breast cancer: irrespective of hormone receptor, Human epidermal growth factor receptor 2 (HER2) status or molecular subtype.
• Non-small cell lung cancer (NSCLC): irrespective of histological or molecular subtypes.
• Ovarian cancer: patients with high-grade serous ovarian cancer (HGSOC).
• Colon cancer: irrespective of molecular subtype.
• Other solid tumor: Patients with any other histology (any molecular subtype) with the exception of primary brain tumors, as well as cutaneous, mucosal, and ocular/uveal melanoma.
• Patients who have previously undergone tumor resection or biopsy and for whom pre-REP TILs are already available and adequate for further REP expansion. The following conditions have to be met:
• a. The Manufacturing facility / sponsor representative confirms that adequate pre-REP material (in quantity and quality) is available to move to REP.
• At least one lesion accessible to biopsy for translational research (TR) at baseline and D30, without putting the patient at unusual risk. Every effort should be made to obtain a fresh tumor biopsy upon enrolment, if previous collection of tissue is judged insufficient for study translational endpoints. The following exceptions are accepted for the baseline biopsy:
• a. Tumor material was properly collected for all protocol translational endpoints during harvesting surgery or biopsy for the TIL production (pre-REP) and no intercurrent anticancer therapy has been administered since that surgery or last biopsy. If patient has been treated with any antitumor therapy that may have altered the tumor microenvironment at the estimation of the PI, a repeat biopsy should be performed.
• Male or female age ≥ 18 to ≤ 70 years at the time of informed consent. Patients aged \>70 will be evaluated by the investigator, and decision will be made according to patient's status, upon agreement with the PI.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) of 0 to 2.
• Life expectancy of greater than 12 weeks.
• Radiologically measurable disease (as per RECIST v1.1).
• Modified RECIST should be used for mesothelioma.

You may not qualify if:

• Patients with an active second malignancy, except for
• non-melanoma skin cancer that has been apparently cured or successfully resected
• carcinoma in situ as long as they have been adequately treated
• Any malignancy that can be adequately managed expectantly without compromising prognosis, and after PI agreement..
• Patients who have a history of malignancy are not considered to have an active malignancy if they have completed therapy since at least 2 years and are considered by their treating investigator to be at ≤ 30% risk for relapse.
• Patients with known peritoneal metastases who have a recent history of intermittent bowel obstruction (even partial), unless such obstruction has been resolved. Agreement with the Trial Chair is mandatory.
• Patients with leptomeningeal carcinomatosis
• History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin)
• History of recent myocardial infarction or unstable angina, either within six months of enrolment
• Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction
• Active severe systemic infections within four weeks prior to beginning of NMA chemotherapy.
• Patient requiring regular systemic immunosuppressive therapy (for example for organ transplantation, chronic rheumatologic disease); all immunosuppressive medications including but not limited to steroids, mycophenolate mofetil, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (TNF)-alpha agents must have been discontinued within the last two weeks prior to starting NMA chemotherapy.
• Note: Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is permitted
• Note: The use of physiologic corticosteroid replacement therapy is permitted.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

CHUV Oncology Department

Lausanne, Canton of Vaud, 1011, Switzerland

Location

MeSH Terms

Interventions

Cyclophosphamide; fludarabine; Interleukin-2; Radiotherapy

Intervention Hierarchy (Ancestors)

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

Study Officials

• George Coukos, MD, PhD

  Department director

  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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: September 1, 2019
• Primary Completion: March 5, 2021
• Study Completion: March 5, 2021
• Last Updated: March 18, 2021

Record last verified: 2021-03

Locations

CH (1)