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

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ClinicalTrials.gov Identifier: NCT02926053
Recruitment Status : Recruiting
First Posted : October 6, 2016
Last Update Posted : March 5, 2018
Sponsor:
Information provided by (Responsible Party):
Inge Marie Svane, Herlev Hospital

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.


Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma Procedure: Surgical removal of tumor tissue for T cell production Drug: Cyclophosphamide Drug: Fludarabine Biological: TIL infusion Drug: Interleukin-2 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: T Cell Therapy for Patients With Metastatic Renal Cell Carcinoma
Study Start Date : December 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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).

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Objective response rate [ Time Frame: Up to 12 months ]
    Clinical responses will be evaluated by RECIST 1.1.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02926053


Contacts
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Contact: Inge Marie Svane, Prof., MD +4538683868 inge.marie.svane@regionh.dk
Contact: Magnus Pedersen, MD +4538683868 magnus.pedersen@regionh.dk

Locations
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Denmark
Center for Cancer Immune Therapy Dept. of Hematology/oncology Recruiting
Herlev, Denmark, 2730
Contact: Inge Marie, Prof., MD    +4538683868    inge.marie.svane@regionh.dk   
Contact: Magnus Pedersen, MD    +4538683868    magnus.pedersen@regionh.dk   
Sponsors and Collaborators
Inge Marie Svane
Investigators
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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

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Responsible Party: Inge Marie Svane, MD, Professor, Herlev Hospital
ClinicalTrials.gov Identifier: NCT02926053     History of Changes
Other Study ID Numbers: UG1617
First Posted: October 6, 2016    Key Record Dates
Last Update Posted: March 5, 2018
Last Verified: March 2018
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents