Peginterferon and TIL Therapy for Metastatic Melanoma
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|ClinicalTrials.gov Identifier: NCT02379195|
Recruitment Status : Completed
First Posted : March 4, 2015
Results First Posted : January 22, 2020
Last Update Posted : January 22, 2020
Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from the 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 are administered to support T cell activation and proliferation in vivo.
In this trial the therapy is combined with peginterferon (the pegylated form of interferon alpha 2b). Interferon alpha has immunomodulatory effects and is known to upregulate HLA expression on melanoma cells and are hypothesized to synergize with TIL therapy.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Melanoma||Drug: Cyclophosphamide Drug: Fludarabine Biological: TIL infusion Drug: Interleukin-2 Drug: Peginterferon alfa-2b||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||T Cell Therapy in Combination With Peginterferon for Patients With Metastatic Melanoma|
|Actual Study Start Date :||November 2014|
|Actual Primary Completion Date :||January 2018|
|Actual Study Completion Date :||October 2018|
All patients receive the same treatment.
All patients are hospitalized during treatment (approximately 3 weeks) 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 are administered on day 0 to day 5.
Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days
Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14)
Cyclophosphamide 60 mg/kg are administered i.v on day -7 and -6
Fludarabine 25 mg/m2 are administered i.v on day -5 to -1
Biological: TIL infusion
The maximum number of expanded TILs are infused over 30-45 min on day 0
Other Name: T cell infusion
Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Drug: Peginterferon alfa-2b
Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
Other Name: PegIntron
- Number of Participants With Adverse Events/Serious Adverse Events [ Time Frame: 0-24 weeks ]Determine the safety of the administration of peginterferon in combination with TIL therapy including lymphodepleting chemotherapy and Interleukin-2 by reporting adverse events according to CTCAE v. 4.0
- Treatment Related Immune Responses [ Time Frame: Up to 12 months ]Number of participants with detectable in vitro immune responses in the TIL infusion product using intracellular flow cytometry.
- Objective Response Rate [ Time Frame: Up to 36 months ]Clinical responses will be evaluated by RECIST 1.1 (Response Criteria In Solid Tumors Criteria version 1.1) and assessed by CT scan. Complete response (CR), disapperance of all lesions; Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective response (OR) = CR + PR
- Overall Survival [ Time Frame: Up to 36 months ]Overall survival (OS), defined as time from treatment initiation to death, described using the Kaplan Meier method
- Progression Free Survival [ Time Frame: Up to 36 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 the Kaplan Meier method.
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): NCT02379195
|Center for Cancer Immune Therapy, Dept. of Haematology/Oncology|
|Copenhagen, Herlev, Denmark, 2730|
|Study Director:||Inge Marie Svane, Prof, PhD, MD||Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark|
|Principal Investigator:||Rikke Andersen, MD||Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark|