TIL Therapy for Metastatic Renal Cell Carcinoma

NCT02926053 | Completed Phase 1 Results DMC

• 1 other identifier: UG1617
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo. Recent studies suggest, that TIL therapy works in other cancers than Metastatic Melanoma, including Renal Cell Carcinoma. In this study TIL therapy is administered to patients with metastatic Renal Cell Carcinoma.

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Patients in Which the Treatment Was Tolerable

  Determine the safety of the administration of TIL therapy including lymphodepleting chemotherapy and Interleukin-2 for patients with metastatic renal cell cancer. This will be assessed clinically by whether the patients are able to receive treatment as described in the protocol.

  0-24 weeks

Secondary Outcomes (2)

• Number of Infusion Products With Detectable in Vitro Anti-tumor Responses

  Up to 12 months

• Objective Response Rate

  Up to 12 months

Study Arms (1)

Patient group

EXPERIMENTAL

All patients receive the same treatment. Surgical removal of tumor tissue for T cell production, which takes 4-6 weeks, is performed initially. All patients are hospitalized during treatment (one week in advance of the T cell product being ready and for approximately 3 weeks in total) and receive treatment only once. The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine on day -7 to day -1. The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered as high-dose i.v. bolus every eight hour starting approximately 6 hours after TIL infusion and for up to 5 days (maximum of 15 doses).

Procedure: Surgical removal of tumor tissue for T cell production; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: TIL infusion; Drug: Interleukin-2

Interventions

Surgical removal of tumor tissue for T cell production PROCEDURE

Surgical removal of \> 1 cm3 tumor tissue chosen with regards to high rate of success and to minimize the general risks involved in a surgical procedure.

Patient group

Cyclophosphamide DRUG

Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.

Also known as: Cyclophospamide

Patient group

Fludarabine DRUG

Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration.

Also known as: Fludarabinephosphate, Fludara

Patient group

TIL infusion BIOLOGICAL

The maximum number of expanded TILs are infused over 30-45 minutes on day 0.

Also known as: T Cell infusion

Patient group

Interleukin-2 DRUG

Interleukin-2 is administered as high-dose bolus infusions (600.000 IU/kg) over a 15 minute period every 8 hours and continuing for up to 5 days (maximum of 15 doses).

Also known as: IL-2, Proleukin

Patient group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological proven mRCC with the possibility of surgical removal of tumor tissue of \> 1 cm3. Histology must include a clear cell component with or without a sarcomatoid dedifferentiation.
• Metastatic disease irrespective of number of previous treatment lines. Treatment naïve pt's can be included.
• ECOG performance status of ≤1.
• IMDC prognostic group 'Favorable' or 'Intermediary'.
• Life expectancy of \> 6 months.
• At least one measurable parameter after surgery in accordance with RECIST 1.1 -criteria's.
• No significant toxicities or side effects (CTC ≤ 1) from previous treatments.
• Normal ejection fraction (EF) measured by a multigated acquisition (MUGA) scan.
• Crom EDTA clearance \>40 ml/min.
• Adequate renal, hepatic and hematological function.
• LDH ≤ 5 times upper normal limit as a measure of tumor burden.
• Able to comprehend the information given and willing to sign informed consent.
• Willingness to participate in the planned controls.

You may not qualify if:

• A history of prior malignancies, except curatively treated non-melanoma skin cancer and CIS of the cervix uteri. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 3 years after treatment.
• Patients with cerebral metastases.
• Patients with widespread bone or bone only metastases.
• Severe allergies, history of anaphylaxis or known allergies to the administered drugs.
• Severe medical conditions or psychiatric comorbidity.
• Acute/chronic infection with HIV, hepatitis, tuberculosis among others.
• Severe and active autoimmune disease.
• Pregnant women and women breastfeeding.
• Simultaneous treatment with systemic immunosuppressive drugs (including prednisolone, methotrexate among others).
• Simultaneous treatment with other experimental drugs.
• Simultaneous treatment with other systemic anti-cancer treatments.
• Patients with active and uncontrollable hypercalcaemia.

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (1)

Center for Cancer Immune Therapy Dept. of Hematology/oncology

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

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

Limitations and Caveats

The trial was designed to include six patients, but due to very slow recruitment the trial only included five patients which is an obvious limitation of the trial and limits.

Results Point of Contact

• Title: Troels Holz Borch, MD, PhD, principal investigator
• Organization: National Center of Cancer Immune Therapy, Department of Oncology

troels.holz.borch@regionh.dk

004524460492

Study Officials

• Inge M Svane, Prof., MD

  Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Borgmester Ib Juuls vej 25C, DK-2730

  STUDY DIRECTOR

• Troels H Borch, MD, PhD

  Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Borgmester Ib Juuls vej 25C, DK-2730

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Professor

Study Record Dates

• First Submitted: October 5, 2016
• First Posted: October 6, 2016
• Study Start: December 1, 2016
• Primary Completion: October 31, 2021
• Study Completion: October 31, 2021
• Last Updated: November 22, 2024
• Results First Posted: November 22, 2024

Record last verified: 2024-09

Locations

DK (1)