Use of IL-15 After Chemotherapy and Lymphocyte Transfer in Metastatic Melanoma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01369888
First received: June 8, 2011
Last updated: June 3, 2014
Last verified: May 2014
  Purpose

Background:

- Researchers have developed an experimental cancer treatment called cell therapy. White blood cells called lymphocytes are taken from a tumor, grown in large numbers in the lab, and then given back to the patient. Interleukin-15, given to the patient after the cells (now called Young tumor-infiltrating lymphocytes of Young TIL cells) are replaced, helps the cells to grow and boosts the immune system. This process changes your normal cells into cells that are able to recognize your tumor has been studied in the lab. These cells can destroy tumor cells in the test tube, but scientists want to see if they work inside the body.

Objectives:

-To test the effectiveness of lymphocytes drawn from tumor cells combined with interleukin-15 in treating metastatic melanoma.

Eligibility:

  • Patients must be 18 - 66 years of age and have a diagnosis of metastatic melanoma.
  • They will have heart and lung function tests, lab tests, and imaging procedures.
  • Patients may not have conditions such as active systemic infections, blood clotting disorders, or other active major medical illnesses.
  • Patients may not be pregnant or nursing.

Condition Intervention Phase
Metastatic Melanoma
Skin Cancer
Drug: Cyclophosphamide
Drug: Fludarabine
Biological: Tumor Infiltrating Lymphocytes
Drug: IL-15
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of IL-15 Administration Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen and Autologous Lymphocyte Transfer in Metastatic Melanoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To determine the safety/toxicity/MTD of intravenous recombinant IL-15 as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy and ACT TIL. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determination of the level of reconstitution of T reg cells in patients who receive cell transfer followed by IL-15 and to determine the PK of IL-15 levels in the serum following intravenous administration. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: May 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cyclophosphamide
    50 mg/m2, IV(in the vein)on day 5 of each 25 day cycle
    Drug: Fludarabine
    25 mg/m2/day IVPB daily over 30 minutes for 5 days (days -5 to -1)
    Biological: Tumor Infiltrating Lymphocytes
    IV over 30 minutes on day 0
    Drug: IL-15
    IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 66 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Measurable metastatic melanoma with available autologous TIL.
    2. Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.
    3. Greater than or equal to 18 years of age and less than or equal to age 66.
    4. Able to understand and sign the Informed Consent Document
    5. Clinical performance status of ECOG 0 or 1.
    6. Life expectancy of greater than three months.
    7. 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 receiving the preparative regimen.
    8. Serology:

      1. 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 be less responsive to the experimental treatment and more susceptible to its toxicities.)
      2. 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.
      3. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
    9. Hematology:

      1. Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim.
      2. WBC (> 3000/mm(3)).
      3. Platelet count greater than 100,000/mm(3).
      4. Hemoglobin greater than 8.0 g/dl.
    10. Chemistry:

      1. Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
      2. Serum creatinine less than or equal to 1.6 mg/dl.
      3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
    11. 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 or as specified in the eligibility criteria.

    12. 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, at the time the patient receives the preparative regimen to allow antibody levels to decline.
    13. Patients who have previously received any anti-CTLA4 antibody and have documented GI toxicity must have a normal colonoscopy with normal colonic biopsies.

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. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  4. 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).
  5. Concurrent systemic steroid therapy.
  6. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  7. Any patient known to have an LVEF less than or equal to 45%.
  8. In patients > 60 years old, documented LVEF of less than or equal to 45%.
  9. Documented LFEV of less than or equal to 45% tested in patients with:

    1. clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or.
    2. age greater than or equal to 60 years old.
  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: NCT01369888

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01369888     History of Changes
Other Study ID Numbers: 110170, 11-C-0170
Study First Received: June 8, 2011
Last Updated: June 3, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immunotherapy
Cell Therapy
IL-15 Cytokine
Melanoma
Metastatic Melanoma
Skin Cancer

Additional relevant MeSH terms:
Melanoma
Skin Neoplasms
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
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014