Trial Outcomes & Findings for TIL Therapy for Metastatic Renal Cell Carcinoma (NCT NCT02926053)

Last Updated: 2024-11-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

5 participants

Primary outcome timeframe

0-24 weeks

Results posted on

2024-11-22

Participant Flow

Participant milestones

Participant milestones
Measure	Patient Group 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). Surgical removal of tumor tissue for T cell production: 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. Cyclophosphamide: Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. Fludarabine: Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration. TIL infusion: The maximum number of expanded TILs are infused over 30-45 minutes on day 0. Interleukin-2: 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).
Overall Study STARTED	5
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patient Group n=5 Participants 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). Surgical removal of tumor tissue for T cell production: 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. Cyclophosphamide: Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. Fludarabine: Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration. TIL infusion: The maximum number of expanded TILs are infused over 30-45 minutes on day 0. Interleukin-2: 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).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Region of Enrollment Denmark	5 participants n=5 Participants

PRIMARY outcome

Timeframe: 0-24 weeks

Outcome measures

Outcome measures
Measure	Patient Group n=5 Participants 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). Surgical removal of tumor tissue for T cell production: 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. Cyclophosphamide: Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. Fludarabine: Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration. TIL infusion: The maximum number of expanded TILs are infused over 30-45 minutes on day 0. Interleukin-2: 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).
Number of Patients in Which the Treatment Was Tolerable	5 Participants

SECONDARY outcome

Timeframe: Up to 12 months

In vitro anti-tumor responses will be measured by cytokine production in a flow-cytometry based assed after co-culture of tumor-infiltrating lymphocytes from the infusion product with autologous tumor cells (from tumor digest and/or autologous tumor cell lines).

Outcome measures

Outcome measures
Measure	Patient Group n=5 Participants 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). Surgical removal of tumor tissue for T cell production: 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. Cyclophosphamide: Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. Fludarabine: Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration. TIL infusion: The maximum number of expanded TILs are infused over 30-45 minutes on day 0. Interleukin-2: 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).
Number of Infusion Products With Detectable in Vitro Anti-tumor Responses	4 Infusion products

SECONDARY outcome

Timeframe: Up to 12 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Outcome measures
Measure	Patient Group n=5 Participants 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). Surgical removal of tumor tissue for T cell production: 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. Cyclophosphamide: Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. Fludarabine: Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration. TIL infusion: The maximum number of expanded TILs are infused over 30-45 minutes on day 0. Interleukin-2: 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).
Objective Response Rate	0 Participants

Adverse Events

Patient Group

Serious events: 1 serious events

Other events: 5 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Patient Group n=5 participants at risk 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). Surgical removal of tumor tissue for T cell production: 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. Cyclophosphamide: Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. Fludarabine: Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration. TIL infusion: The maximum number of expanded TILs are infused over 30-45 minutes on day 0. Interleukin-2: 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).
Blood and lymphatic system disorders Hypotension	20.0% 1/5 • Number of events 1 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.

Other adverse events

Other adverse events
Measure	Patient Group n=5 participants at risk 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). Surgical removal of tumor tissue for T cell production: 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. Cyclophosphamide: Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. Fludarabine: Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration. TIL infusion: The maximum number of expanded TILs are infused over 30-45 minutes on day 0. Interleukin-2: 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).
Blood and lymphatic system disorders Febrile neutropenia	100.0% 5/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Blood and lymphatic system disorders Petechiae	20.0% 1/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Blood and lymphatic system disorders Anemia	100.0% 5/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Respiratory, thoracic and mediastinal disorders Dyspnoe	100.0% 5/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Nervous system disorders Confusional state	40.0% 2/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Nervous system disorders Hallucination	20.0% 1/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
General disorders Fatigue	100.0% 5/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
General disorders Pain	80.0% 4/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
General disorders Performance status decreased	100.0% 5/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
General disorders Weight increased	20.0% 1/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Gastrointestinal disorders Constipation	60.0% 3/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Gastrointestinal disorders Diarrhoea	80.0% 4/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Gastrointestinal disorders Nausea	100.0% 5/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Gastrointestinal disorders Stomatitis	60.0% 3/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Gastrointestinal disorders Vomiting	40.0% 2/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Gastrointestinal disorders Melaena	20.0% 1/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	40.0% 2/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Skin and subcutaneous tissue disorders Dry skin	100.0% 5/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Musculoskeletal and connective tissue disorders Myalgia	60.0% 3/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.
Infections and infestations Infection	80.0% 4/5 • Adverse events were collected continuously during the trial from inclusion to end-of-study visit, up to 9 months.

Additional Information

Troels Holz Borch, MD, PhD, principal investigator

National Center of Cancer Immune Therapy, Department of Oncology

Phone: 004524460492

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place