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

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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