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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT02621021
First received: December 2, 2015
Last updated: December 13, 2016
Last verified: December 2016
  Purpose

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

Design:

Participants will be screened with:

Physical exam

CT, MRI, or PET scans

X-rays

Heart and lung function tests

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

Possible filgrastim injection

Recovery for 1 2 weeks

After treatment, participants will:

Take an antibiotic and antiviral for at least 6 months

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


Condition Intervention Phase
Melanoma
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Aldeslaukin
Drug: Pembrolizumab
Biological: young TIL
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To determine in a prospective randomized trial whether the addition of pembrolizumab to the standard nonmyeloablative conditioningregimen, TIL and high dose IL-2 (ACT TIL) can improve complete response rates in patients with metastatic melano... [ Time Frame: approximately 3-4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 170
Study Start Date: November 2015
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm1
non-myeloablative chemotherapy regimen followed byTIL and IL-2.
Drug: Cyclophosphamide
Days -7 and -6, Cyclophosphamide 60 mg/kg/day IV in 250 ml D5W with mesna 15 mg/kg/day over 1 hr X 2 days.
Drug: Fludarabine
Days -7 to -3, Fludarabine 25 mg/m2/day IVPB daily over 15-30 minutes for 5 days.
Drug: Aldeslaukin
Day 0 (within 24 hours of cell infusion), Aldesleukin 720,000 IU/kg (based on total body weight) IV over a 15 minute infusion and continuing for up to 4 days (maximum 12 doses).
Biological: young TIL
Day 0 (two to four days after last dose of fludarabine), cells will be administered intravenously over 20 to 30 minutes.
Experimental: Arm2
standard non-myeloablative chemotherapy regimen,pembrolizumab, the TIL product and IL-2.
Drug: Cyclophosphamide
Days -7 and -6, Cyclophosphamide 60 mg/kg/day IV in 250 ml D5W with mesna 15 mg/kg/day over 1 hr X 2 days.
Drug: Fludarabine
Days -7 to -3, Fludarabine 25 mg/m2/day IVPB daily over 15-30 minutes for 5 days.
Drug: Aldeslaukin
Day 0 (within 24 hours of cell infusion), Aldesleukin 720,000 IU/kg (based on total body weight) IV over a 15 minute infusion and continuing for up to 4 days (maximum 12 doses).
Drug: Pembrolizumab
Day -2, day 21, day 42, and day 63, Pembrolizumab 2mg/kg IV over approximately 30 minutes.
Biological: young TIL
Day 0 (two to four days after last dose of fludarabine), cells will be administered intravenously over 20 to 30 minutes.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Senior)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  1. Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation.
  2. Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of NCI.
  3. Patients must have received at least one prior therapy for metastatic melanoma.
  4. 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.
  5. Greater than or equal to 16 years of age and less than or equal to 70 years of age.
  6. All participants and/or their parents or legally authorized representatives must sign a written informed consent. Assent will be obtained for all participants under the age of 18 years.
  7. All participants 18 years of age or older must be willing to sign a durable power of attorney
  8. Clinical performance status of ECOG 0 or 1.
  9. Life expectancy of greater than three months.
  10. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment.
  11. 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.
  12. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
  13. Hematology

    • Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim
    • WBC greater than or equal to 3000/mm3
    • Platelet count greater than or equal to 100,000/mm3
    • Hemoglobin > 8.0 g/dl
  14. Chemistry:

    • Serum ALT/AST less than or equal to 2.5 times the upper limit of normal
    • Serum Creatinine less than or equal to 1.6 mg/dl
    • Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert s Syndrome who musthave a total bilirubin less than 3.0 mg/dl.
  15. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).(Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less)
  16. patients must demonstrate progressive disease at the time of treatment.(Note: Patients who have received tyrosine kinase inhibitors (e.g. vemurafinib) may be treated if they present with stable disease at the time of treatment)
  17. Six weeks must have elapsed from the time of any antibody therapy that could affect an anti cancer immune response, including anti-CTLA4 antibody therapy and anti PD-1/PD-L1 agents, at the time the patient receives the preparative regimen to allow antibody levels to decline.

EXCLUSION CRITERIA:

  1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
  2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency

    Disease).

  3. 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).
  4. Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  5. History of major organ autoimmune disease
  6. Concurrent systemic steroid therapy.
  7. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  8. Grade 3 or 4 Major organ Immune-related Adverse Events (IRAEs) following treatment with anti PD-1/PD-L1.
  9. History of coronary revascularization or ischemic symptoms.
  10. Documented LVEF of less than or equal to 45%; note: testing is required in patients with:

    • Age > 65 years old
    • Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02621021

Contacts
Contact: Ellen Bodurian (866) 820-4505 ncisbirc@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center    866-820-4505    ncisbirc@mail.nih.gov   
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02621021     History of Changes
Other Study ID Numbers: 160027  16-C-0027 
Study First Received: December 2, 2015
Last Updated: December 13, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Melanoma
Skin Cancer
Immunotherapy
Cell Therapy

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Pembrolizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on January 14, 2017