Adoptive Cell Therapy Following a Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in combination with lymphodepletion and high-dose interleukin 2 (IL-2) has demonstrated reproducible objective response rates of approximately 50 percent in patients with highly advanced, refractory metastatic melanoma.
Recent developments in theTIL ACT procedure facilitate the use of a reduced-intensity, non-myeloablative, lympho-depleting preparative regimen which is expected to be both less toxic and equally efficient compared to previous regimens.
|Malignant Melanoma Stage IV||Drug: Fludarabine Radiation: Radiation Biological: TIL Drug: IL-2||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients|
- Objective tumor responses [ Time Frame: 3 years ]Radiological follow up via CT to determine the sum of Complete Responders (CR) + Partial Responders (PR) + Stable Disease (SD) as assessed by RECIST 1.1
- Assess adverse events using NCI CTCAE v4.03 during treatment and follow-up [ Time Frame: 3 years ]Adverse events will be assessed using NCI CTCAE v4.03 during treatment and follow-up
- Overall Survival (OS) [ Time Frame: 3 years ]Overall survival is defined as the time from study entry until death from any cause
- Response Rate (RR) [ Time Frame: 3 years ]Radiological follow up via CT to determine the sum of Complete Responders (CR) + Partial Responders (PR) as assessed by RECIST 1.1
- Progression-Free Survival (PFS) [ Time Frame: 3 years ]Progression free survival according to RECIST 1.1
- Quality of Life (QoL) [ Time Frame: 3 years ]Assessment of QoL using the EORTC QLQ-MEL38 instrument (specific for Melanoma)
|Anticipated Study Start Date:||June 1, 2017|
|Estimated Study Completion Date:||June 1, 2021|
|Estimated Primary Completion Date:||June 1, 2020 (Final data collection date for primary outcome measure)|
Experimental: ACT TIL
Reduced intensity, myeloablative, lymphodepleting regimenRadiation: Radiation
Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 dayBiological: TIL
TIL administrationDrug: IL-2
Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
The Sponsor is developing the ex-vivo expanded autologous TIL as the Investigational Product (IP). Yet, the administration of the TIL cellular product can only be accomplished in the context of an autologous, Adoptive Cell Therapy (ACT) procedure which is composed of the following steps:
- Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
- Bolus high-dose (720,000 IU/kg) IL-2, which will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
- Early-stage follow-up until 30 days post-discharge
- Late-stage follow-up, such as CT scans, will be carried out four and twelve weeks after TIL administration, and then every 3 months thereafter for the first year after TIL therapy; for the second year and onwards, as clinically indicated.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03166397
|Contact: Meital Barfirstname.lastname@example.org|
|Sheba Medical Center||Recruiting|
|Ramat Gan, Israel, 5262100|
|Contact: Meital Bar 972-3-5305201 email@example.com|
|Principal Investigator: Jacob Schachter, MD|