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

Sponsor
Sheba Medical Center
Study ID
NCT03166397
Phase
PHASE2
Status
Unknown

Conditions

  • Malignant Melanoma Stage IV

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Fludarabine — DRUG
    Cyclophosphamide 30mg/kg/day with Fludarabine (25 mg/m2/d) followed by 3 consecutive days of Fludarabine 25mg/m2/d.
  • Cyclophosphamide — DRUG
    Cyclophosphamide 30mg/kg/day with Fludarabine (25 mg/m2/d) followed by 3 consecutive days of Fludarabine 25mg/m2/d.
  • TIL — BIOLOGICAL
    TIL administration
  • IL-2 — DRUG
    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 — DRUG
    Nivolumab 480 mg fixed dose
  • Ipilimumab — DRUG
    Ipilimumab 1 mg/kg up to 100 mg
  • FMT Protocol — DRUG
    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.

Study Details

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.

Key Dates

First listed
May 25, 2017
Start date
Jun 5, 2017
Status verified
Jan 2023
Primary completion
Jan 1, 2025
Completion
Jun 1, 2026

Study Design

Enrollment
30 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: ACT TIL
    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. Preparation and administration of TIL 3. 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.
  • Experimental: ACT TIL + Anti PD-1
    1. Single dose of Nivolumab 480 mg fixed dose 2. 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.. 3. Preparation and administration of TIL 4. 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. 5. Second dose of Nivolumab 480 mg fixed dose (at least 4 weeks from the first dose)
  • Experimental: ACT TIL FMT + Anti CTLA4
    1. FMT loading dose given via colonoscopy 2. FMT 12 oral capsules as maintenance - given 2 times 3. Single dose of Ipilimumab 1mg/kg up to 100 mg 4. 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.. 5. Preparation and administration of TIL 6. 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.

Primary Outcome Measure

Objective tumor responses [ Time Frame: 3 years ]

Central Contacts

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