NCT03166397

Adoptive Cell Therapy Following a Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Sheba Medical Center · Other Government
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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: 1. Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Cyclophosphamide 30mg/kg/day with Fludarabine (25 mg/m2/d) followed by 3 consecutive days of Fludarabine 25mg/m2/d. 2. 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. 3. Early-stage follow-up until 30 days post-discharge 4. 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. Recently 2 new arms were, using the same protocol described above with the following additions: Arm 2 - TIL-ACT + Anti PD-1 -the addition of 2 doses of Nivolumab fixed dose 480mg, pre and post TIL. Arm 3 - TIL-ACT with FMT + Anti CTLA4 - the addition of 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.

Conditions

• Malignant Melanoma Stage IV

Interventions

Type	Name	Description
DRUG	Fludarabine	Cyclophosphamide 30mg/kg/day with Fludarabine (25 mg/m2/d) followed by 3 consecutive days of Fludarabine 25mg/m2/d.
DRUG	Cyclophosphamide	Cyclophosphamide 30mg/kg/day with Fludarabine (25 mg/m2/d) followed by 3 consecutive days of Fludarabine 25mg/m2/d.
BIOLOGICAL	TIL	TIL administration
DRUG	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.
DRUG	Nivolumab	Nivolumab 480 mg fixed dose
DRUG	Ipilimumab	Ipilimumab 1 mg/kg up to 100 mg
DRUG	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.

Timeline

• Start date: 2017-06-05
• Primary completion: 2025-01-01
• Completion: 2026-06-01
• First posted: 2017-05-25
• Last updated: 2023-01-26

Locations

1 site across 1 country: Israel