Back to resultsTIL Therapy for Metastatic Renal Cell Carcinoma
Primary Purpose
Metastatic Renal Cell Carcinoma
Status
Unknown status
Phase
Phase 1
Locations
Denmark
Study Type
Interventional
Intervention
Surgical removal of tumor tissue for T cell production
Cyclophosphamide
Fludarabine
TIL infusion
Interleukin-2
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Renal Cell Carcinoma
Eligibility 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.
Sites / Locations
- Center for Cancer Immune Therapy Dept. of Hematology/oncologyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Patient group
Arm Description
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).
Outcomes
Primary Outcome Measures
Number and type of reported adverse events
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
Treatment related immune responses
To evaluate the immunological impact of TIL therapy for patients with metastatic Renal Cell Carcinoma.
Objective response rate
Clinical responses will be evaluated by RECIST 1.1.
Overall Survival
Overall Survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.
Progression free survival
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02926053
Brief Title
TIL Therapy for Metastatic Renal Cell Carcinoma
Official Title
T Cell Therapy for Patients With Metastatic Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 2016 (undefined)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Inge Marie Svane
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Patient group
Arm Type
Experimental
Arm Description
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).
Intervention Type
Procedure
Intervention Name(s)
Surgical removal of tumor tissue for T cell production
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cyclophospamide
Intervention Description
Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludarabinephosphate, Fludara
Intervention Description
Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration.
Intervention Type
Biological
Intervention Name(s)
TIL infusion
Other Intervention Name(s)
T Cell infusion
Intervention Description
The maximum number of expanded TILs are infused over 30-45 minutes on day 0.
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
IL-2, Proleukin
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number and type of reported adverse events
Description
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.
Time Frame
0-24 weeks
Secondary Outcome Measure Information:
Title
Treatment related immune responses
Description
To evaluate the immunological impact of TIL therapy for patients with metastatic Renal Cell Carcinoma.
Time Frame
Up to 12 months
Title
Objective response rate
Description
Clinical responses will be evaluated by RECIST 1.1.
Time Frame
Up to 12 months
Title
Overall Survival
Description
Overall Survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.
Time Frame
Up to 12 months
Title
Progression free survival
Description
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.
Time Frame
Up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Inge Marie Svane, Prof., MD
Phone
+4538683868
Email
inge.marie.svane@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Magnus Pedersen, MD
Phone
+4538683868
Email
magnus.pedersen@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Inge Marie Svane, Prof., MD
Organizational Affiliation
Center for Cancer Immune Therapy, Dept. of Oncology/Hematology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Magnus Pedersen, MD
Organizational Affiliation
Center for Cancer Immune Therapy, Dept. of Oncology/Hematology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Cancer Immune Therapy Dept. of Hematology/oncology
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Inge Marie, Prof., MD
Phone
+4538683868
Email
inge.marie.svane@regionh.dk
First Name & Middle Initial & Last Name & Degree
Magnus Pedersen, MD
Phone
+4538683868
Email
magnus.pedersen@regionh.dk
12. IPD Sharing Statement
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TIL Therapy for Metastatic Renal Cell Carcinoma
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