A Prospective Randomized and 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

Melanoma Clinical Trial

Official title: A Prospective Randomized and Phase II Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor-Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration of Pembrolizumab

Status Suspended

Clinical Trial 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 18-70 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

Clinical Trial Description

Background:

• Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered along with highdose 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 in a prospective randomized trial whether the addition of pembrolizumab to the standard non-myeloablative conditioning regimen, TIL, and high-dose IL-2 can improve complete response rates in patients with metastatic melanoma who have received prior anti PD-1/PD-L1 therapy (Cohort 1)

• Determine the complete response rate to the standard non-myeloablative conditioning regimen, TIL, and high-dose IL-2 in combination with pembrolizumab in patients with metastatic melanoma who have not received prior anti-PD-1/PD-L1 therapy (Cohort 2)

Eligibility:

• Age greater than or equal to 18 and less than or equal to 70 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 2 cohorts: (1)

• patients who are refractory to prior anti PD-1/PD-L1

• patients who have not received prior anti PD-1/PD-L1

• After TIL growth is established:

• Patients assigned to Cohort 1 will be randomized to either receive or not receive pembrolizumab in combination with the standard non-myeloablative conditioning regimen, TIL and high dose IL-2

• All patients assigned to Cohort 2 will receive the standard nonmyeloablative conditioning regimen, TIL, and high-dose IL-2ACT in combination with pembrolizumab.

• 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 170 patients may be enrolled over 3-4 years. ;

Related Conditions & MeSH terms

• Melanoma

• NCT number: NCT02621021
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Suspended
• Phase: Phase 2
• Start date: December 4, 2015
• Completion date: June 16, 2026