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Trial record 1 of 1 for:    NCT02926053
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TIL Therapy for Metastatic Renal Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02926053
Recruitment Status : Recruiting
First Posted : October 6, 2016
Last Update Posted : December 23, 2019
Sponsor:
Information provided by (Responsible Party):
Inge Marie Svane, Herlev Hospital

Tracking Information
First Submitted Date  ICMJE October 5, 2016
First Posted Date  ICMJE October 6, 2016
Last Update Posted Date December 23, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
Number and type of reported adverse events [ Time Frame: 0-24 weeks ]
Determine the safety of the administration of TIL therapy including lymphodepleting chemotherapy and Interleukin-2 for patients with metastatic Ovarian Cancer by reporting adverse events according to CTCAE v. 4.0.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02926053 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2016)
  • Treatment related immune responses [ Time Frame: Up to 12 months ]
    To evaluate the immunological impact of TIL therapy for patients with metastatic Renal Cell Carcinoma.
  • Objective response rate [ Time Frame: Up to 12 months ]
    Clinical responses will be evaluated by RECIST 1.1.
  • Overall Survival [ Time Frame: Up to 12 months ]
    Overall Survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.
  • Progression free survival [ Time Frame: Up to 12 months ]
    Progression free survival (PFS), defined as the time from treatment initiation to disease progression, relapse or death due to any cause, which ever comes first, will be described with Kaplan Meier curve.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TIL Therapy for Metastatic Renal Cell Carcinoma
Official Title  ICMJE T Cell Therapy for Patients With Metastatic Renal Cell Carcinoma
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.

Detailed Description

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.

Objectives:

To evaluate safety and feasibility when treating patients with metastatic renal cell carcinoma with ACT with TILs.

To evaluate treatment related immune responses . To evaluate clinical efficacy.

Design:

Patients will be screened with a physical exam, medical history, blood samples, pulmonary function test, Cr-EDTA clearance, MUGA scan and ECG.

Patients will undergo surgery to harvest tumor material for TIL production.

Patients is admitted day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7.

On day 0 patients receive TIL infusion and shortly after starts IL-2 administration with high-dose bolus IL-2 every eight hour for up to 5 days (maximum of 15 doses).

The patients will followed until progression or up to 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Renal Cell Carcinoma
Intervention  ICMJE
  • Procedure: 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.
  • Drug: Cyclophosphamide
    Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
    Other Name: Cyclophospamide
  • Drug: Fludarabine
    Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration.
    Other Names:
    • Fludarabinephosphate
    • Fludara
  • Biological: TIL infusion
    The maximum number of expanded TILs are infused over 30-45 minutes on day 0.
    Other Name: T Cell infusion
  • Drug: 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).
    Other Names:
    • IL-2
    • Proleukin
Study Arms  ICMJE Experimental: 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).

Interventions:
  • Procedure: Surgical removal of tumor tissue for T cell production
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
  • Biological: TIL infusion
  • Drug: Interleukin-2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 5, 2016)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • Women in the fertile age must use effective contraception. Likewise, men included in the study, as well as their partners, must use effective contraception. This applies from inclusion and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered safe contraceptives.
  • Able to comprehend the information given and willing to sign informed consent.
  • Willingness to participate in the planned controls.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Inge Marie Svane, Prof., MD +4538683868 inge.marie.svane@regionh.dk
Contact: Magnus Pedersen, MD +4538683868 magnus.pedersen@regionh.dk
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02926053
Other Study ID Numbers  ICMJE UG1617
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Inge Marie Svane, Herlev Hospital
Study Sponsor  ICMJE Inge Marie Svane
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Inge Marie Svane, Prof., MD Center for Cancer Immune Therapy, Dept. of Oncology/Hematology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
Principal Investigator: Magnus Pedersen, MD Center for Cancer Immune Therapy, Dept. of Oncology/Hematology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
PRS Account Herlev Hospital
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP