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Adoptive Cell Therapy Following a Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients
Sponsor: Sheba Medical Center
Summary
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. Recently patients recruited post Anti PD-1 therapy had inferior responses in comparison to the pre immune checkpoint inhibitors era. Therefore 2 new arms were added: 1. TIL-ACT with combination of 2 doses of Nivolumab fixed dose 480mg, pre and post TIL. 2. TIL-ACT with FMT given using colonoscopy once and 2 maintenance doses of 12 orally ingested capsules, concurrently with a single dose of Ipilimumab 1 mg/kg up to 100 mg.
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
Key Details
Gender
All
Age Range
18 Years - 80 Years
Study Type
INTERVENTIONAL
Enrollment
30
Start Date
2017-06-05
Completion Date
2026-06-01
Last Updated
2023-01-26
Healthy Volunteers
No
Conditions
Interventions
Fludarabine
Cyclophosphamide 30mg/kg/day with Fludarabine (25 mg/m2/d) followed by 3 consecutive days of Fludarabine 25mg/m2/d.
Cyclophosphamide
Cyclophosphamide 30mg/kg/day with Fludarabine (25 mg/m2/d) followed by 3 consecutive days of Fludarabine 25mg/m2/d.
TIL
TIL administration
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.
Nivolumab
Nivolumab 480 mg fixed dose
Ipilimumab
Ipilimumab 1 mg/kg up to 100 mg
FMT Protocol
FMT given both directly into the colon via colonoscopy and orally using capsules (12 capsules each time). FMT will be taken from melanoma patients treated with Anti PD-1 who achieved a durable response of more than 12 months.
Locations (1)
Sheba Medical Center
Ramat Gan, Israel