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

NCT02621021 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 16002716-C-0027
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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

Conditions

Melanoma

Keywords

Melanoma; Skin Cancer; Immunotherapy; Cell Therapy

Outcome Measures

Primary Outcomes (1)

• Response rate

  Percentage of patients who have a clinical response to treatment (objective tumor regression)

  6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x 2 years

Secondary Outcomes (4)

• Frequency and severity of treatment-related adverse events

  30 days after end of treatment

• Overall survival

  Time of death

• 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

• Overall survival (Cohort 3, Arm 3)

  Time of death

Study Arms (3)

1/ACT TIL

EXPERIMENTAL

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2)

Biological: young TIL; Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide

2/ACT TIL + Pembro

EXPERIMENTAL

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab

Biological: young TIL; Drug: Pembrolizumab; Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide

3/ACT TIL (Pembro contraindicated)

EXPERIMENTAL

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin (IL-2)

Biological: young TIL; Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

young TIL BIOLOGICAL

Day 0: Cells will be administered intravenously (IV) on the Patient Care Unit over 20-30 minutes.

1/ACT TIL; 2/ACT TIL + Pembro; 3/ACT TIL (Pembro contraindicated)

Pembrolizumab DRUG

(Cohort 1, Arm 2 ,Cohort 2 and Cohort 3, Arm 2) On day -2, and days 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days) following cell infusion: Pembrolizumab 2mg/kg IV over approximately 30 minutes.

2/ACT TIL + Pembro

Aldesleukin DRUG

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).

1/ACT TIL; 2/ACT TIL + Pembro; 3/ACT TIL (Pembro contraindicated)

Fludarabine DRUG

Days -7 to -3, Fludarabine 25 mg/m2/day IVPB daily over 15-30 minutes for 5 days.

1/ACT TIL; 2/ACT TIL + Pembro; 3/ACT TIL (Pembro contraindicated)

Cyclophosphamide DRUG

Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W with mesna 15 mg/kg/day over 1 hour X 2 days.

1/ACT TIL; 2/ACT TIL + Pembro; 3/ACT TIL (Pembro contraindicated)

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation.
• Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of NCI.
• Patients must have received at least one prior therapy for metastatic melanoma.
• Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
• Greater than or equal to 18 years and less than or equal to 72 years.
• All participants must sign a written informed consent.
• All participants must be willing to sign a durable power of attorney
• Clinical performance status of ECOG 0 or 1.
• Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment.
• Serology:
• Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
• Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
• Individuals of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.
• Individuals of child-bearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \[IUD, abstinence, surgical sterilization starting at the time of study entry, for the duration of study therapy, and 12 months after the last dose of combined chemotherapy
• Individuals that can father children must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and for 4 months after the last dose of combined chemotherapy. We also will recommend individuals that can father children ask their partners to be on highly effective birth control (hormonal, intrauterine device (IUD), surgical sterilization).

You may not qualify if:

• Individuals of child-bearing potential who are pregnant or nursing because of the potentially dangerous effects of the treatment on the fetus or infant.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• Active systemic infections requiring anti-infective treatment, coagulation disorders or any other active major medical illnesses.
• History of major organ autoimmune disease
• Concurrent systemic steroid therapy.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Grade 3 or 4 major organ Immune-related Adverse Events (IRAEs) clinically attributed to anti PD-1/PD-L1 monotherapy. Previously screened participants that experience these IRAEs after resection for creation of TIL are excluded from Arm 2, but may be eligible for assignment to Arm 3. NOTE: For the purposes of this protocol, thyroid is not considered a major organ.
• History of coronary revascularization or ischemic symptoms.
• For select patients with a clinical history prompting cardiac evaluation: last LVEF less than or equal to 45%
• For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%.
• Patients who are receiving any other investigational agents.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, Morton KE, Laurencot CM, Steinberg SM, White DE, Dudley ME. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011 Jul 1;17(13):4550-7. doi: 10.1158/1078-0432.CCR-11-0116. Epub 2011 Apr 15.

  PMID: 21498393 BACKGROUND

• Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A; KEYNOTE-006 investigators. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015 Jun 25;372(26):2521-32. doi: 10.1056/NEJMoa1503093. Epub 2015 Apr 19.

  PMID: 25891173 BACKGROUND

• Besser MJ, Shapira-Frommer R, Itzhaki O, Treves AJ, Zippel DB, Levy D, Kubi A, Shoshani N, Zikich D, Ohayon Y, Ohayon D, Shalmon B, Markel G, Yerushalmi R, Apter S, Ben-Nun A, Ben-Ami E, Shimoni A, Nagler A, Schachter J. Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies. Clin Cancer Res. 2013 Sep 1;19(17):4792-800. doi: 10.1158/1078-0432.CCR-13-0380. Epub 2013 May 20.

  PMID: 23690483 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

pembrolizumab; aldesleukin; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Stephanie L Goff, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI/Surgery Branch Recruitment Center

CONTACT

(866) 820-4505; IRC@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2015
• First Posted: December 3, 2015
• Study Start: December 4, 2015
• Primary Completion (Estimated): June 16, 2028
• Study Completion (Estimated): June 16, 2029
• Last Updated: June 8, 2026

Record last verified: 2026-06-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)