A Phase 2 Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration of Pembrolizumab
- Conditions
- Melanoma
- Interventions
- Registration Number
- NCT02621021
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
Cell therapy is an experimental cancer therapy. It takes young tumor infiltrating lymphocytes (Young TIL) cells from a person s tumors and grows them in a lab. Then they are returned to the person. Researchers think adding the drug pembrolizumab might make the therapy more effective.
Objective:
To test if adding pembrolizumab to cell therapy is safe and effective to shrink melanoma tumors.
Eligibility:
People ages 18-72 years with metastatic melanoma OF THE SKIN
Design:
Participants will be screened with:
Physical exam
CT, MRI, or PET scans
X-rays
Heart and lung function tests if indicated
Blood and urine tests
Before treatment, participants will have:
A piece of tumor taken from a biopsy or during surgery in order to grow TIL cells
Leukapheresis: Blood flows through a needle in one arm and into a machine that removes white blood cells.
The rest of the blood returns through a needle in the other arm.
An IV catheter placed in the chest for getting TIL cells, aldesleukin, and pembrolizumab (if assigned)
Participants will stay in the hospital for treatment. This includes:
Daily chemotherapy for 1 week
For some participants, pembrolizumab infusion 1 day after chemotherapy
TIL cell infusion 2-4 days after chemotherapy, then aldesleukin infusion every 8 hours for up to 12 doses
Filgrastim injections to help restore your blood counts
Recovery for 1-3 weeks
After treatment, participants will:
Take an antibiotic and an antiviral for at least 6 months, as applicable
If assigned, have pembrolizumab treatment every 3 weeks for 3 more doses. They may have another round.
Have 2-day follow-up visits every 1-3 months for 1 year and then every 6 months
- Detailed Description
Background:
- Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting
preparative regimen consisting of cyclophosphamide and fludarabine.
- Pembrolizumab, a monoclonal antibody that binds to PD-1 and blocks the PD-1/PD-L1 axis, facilitates the activity of anti-tumor lymphocytes in the tumor micro environment. Pembrolizumab administration can result in objective tumor responses in patients with
metastatic melanoma and is approved for use by the FDA for the treatment of these patients.
* Administered TIL express low levels of PD-1, though PD-1 can be re-expressed on TIL in vivo following TIL administration.
* In pre-clinical models, the administration of an anti-PD1 antibody enhances the anti-tumor activity of transferred T-cells.
Objectives:
Primary Objectives:
Determine the objective response rate with the addition of
pembrolizumab to the standard non-myeloablative conditioning regimen, TIL, and
high-dose IL-2 in patients with metastatic melanoma who have received prior anti-
PD-1/PD-L1 therapy (Cohorts 1 and 3).
Eligibility:
* Age greater than or equal to 18 and less than or equal to 72 years
* Evaluable metastatic melanoma
* Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL
* No allergies or hypersensitivity to high-dose aldesleukin administration
* No concurrent major medical illnesses or any form of immunodeficiency
Design:
* Patients with metastatic melanoma will have lesions resected for TIL
* Patients will be assigned one of 3 cohorts: (1) patients who are refractory to prior
anti-PD-1/PD-L1 therapy (randomized); (2) patients who have not received prior anti-
PD-1/PD-L1 therapy; and (3) patients who are refractory to anti PD-1/PD-L1 (nonrandomized).
Note: Cohorts 1 and 2 were closed upon the addition of Cohort 3.
* After TIL growth is established: Patients assigned to Cohort 3 without contraindications to pembrolizumab, will be assigned to receive pembrolizumab in combination with the standard non-myeloblative (NMA) conditioning regimen, TIL, and high-dose IL-s (Arm 2). Patients in Cohort 3 with relative contraindicatioons to prembrolizumab will be assigned to receive standard NMA, TIL, and high dose IL-2 (Arm 3).
* For those patients receiving pembrolizumab- Pembrolizumab will be administered immediately prior to TIL administration and continue for an additional three cycles following the cell infusion.
* Up to 53 patients may be enrolled over 3-4 years.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1/ACT TIL young TIL Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) 1/ACT TIL Aldesleukin Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) 1/ACT TIL Fludarabine Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) 1/ACT TIL Cyclophosphamide Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) 2/ACT TIL + Pembro young TIL Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab 2/ACT TIL + Pembro Pembrolizumab Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab 2/ACT TIL + Pembro Aldesleukin Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab 2/ACT TIL + Pembro Fludarabine Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab 2/ACT TIL + Pembro Cyclophosphamide Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab 3/ACT TIL (Pembro contraindicated) young TIL Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin (IL-2) 3/ACT TIL (Pembro contraindicated) Aldesleukin Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin (IL-2) 3/ACT TIL (Pembro contraindicated) Fludarabine Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin (IL-2) 3/ACT TIL (Pembro contraindicated) Cyclophosphamide Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin (IL-2)
- Primary Outcome Measures
Name Time Method Response rate 6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x 2 years Percentage of patients who have a clinical response to treatment (objective tumor regression)
- Secondary Outcome Measures
Name Time Method Frequency and severity of treatment-related adverse events 30 days after end of treatment Aggregate of all adverse events, as well as their frequency and severity
Overall survival Time of death Time from start of treatment to death from any cause
Objective response rate (ORR), progression free survival (PFS) and safety (Cohort 3, Arm 3) 6 and 12 weeks after cell infusion, then every 3 months x 3, then every 6 months x 2 years Percentage of patients who have a complete response and/or partial response to treatment
Overall survival (Cohort 3, Arm 3) Time of death Time from start of treatment to death from any cause
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States