Chemotherapy Followed by gp100 Lymphocytes and Aldesleukin to Treat Melanoma

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00665470
First received: April 23, 2008
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

Background:

This study uses a new experimental procedure for treating melanoma that uses the patient's own lymphocytes (type of white blood cell), which are specially selected to target and destroy their tumor.

Objectives:

To determine whether this experimental treatment can cause the patient's tumor to shrink.

To test the safety of the treatment and its effects on the immune system.

Eligibility:

Patients with metastatic melanoma 18 years of age and older for whom standard treatments are not effective or who cannot take high-dose interleukin-2 (IL-2).

Patients must have the tissue type human leukocyte antigens (HLA-A)0201.

Design:

Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.

Patients have leukapheresis (a procedure for collecting lymphocytes that is similar to collecting whole blood) to collect cells for laboratory treatment and later reinfusion.

Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to receive the cultured lymphocytes.

Cell infusion and IL-2 treatment: Patients receive the lymphocytes by infusion through a vein and then either high-dose IL-2 infused through a vein or low-dose IL-2 injected under the skin. High-dose IL-2 is given as infusions through a vein every 8 hours for up to 15 doses. Low-dose IL-2 is given as injections under the skin daily for 5 days, followed by a 2-day rest, with this regimen repeated for a total of 5 weeks.

Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and IL-2.

Tumor biopsy: Patients may be asked to have a biopsy (removal of a small piece of tumor) after receiving treatment to look at the effects of treatment in the tumor.

Follow-up: After treatment is completed, patients return to the clinic for physical examinations, review of side effects, laboratory tests and scans every 1 to 6 months until the disease worsens.

Retreatment: Patients whose tumor did not grow after treatment or showed evidence of shrinking may be able to be retreated if their tumor begins to grow. They receive the same regimen of chemotherapy, lymphocyte infusion and IL-2 treatment....


Condition Intervention Phase
Skin Cancer
Metastatic Melanoma
Drug: Aldesleukin
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: Phase II Study in Patients With Metastatic Melanoma Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of gp100 Reactive Peripheral Blood Lymphocytes (PBL) and High or Low Dose Aldesleukin

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.

  • Toxicity as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V3.0 [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For a detailed list of participants with adverse events, see the adverse event module.


Enrollment: 10
Study Start Date: April 2008
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort I - high dose Aldesleukin
Patients receive high-dose aldesleukin intravenous (IV) over 15 minutes every 8 hours beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion and continuing for up to 5 days (maximum of 15 doses).
Drug: Aldesleukin

High-dose aldesleukin intravenous (IV) over 15 minutes every 8 hours beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion and continuing for up to 5 days (maximum of 15 doses).

Receive low-dose aldesleukin subcutaneously (SC) once daily 5 days a week for up to 6 weeks

Experimental: Cohort II - low dose Aldesleukin
Beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion, patients receive low-dose aldesleukin subcutaneous (SC) once daily 5 days a week for up to 6 weeks.
Drug: Aldesleukin

High-dose aldesleukin intravenous (IV) over 15 minutes every 8 hours beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion and continuing for up to 5 days (maximum of 15 doses).

Receive low-dose aldesleukin subcutaneously (SC) once daily 5 days a week for up to 6 weeks


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  1. Measurable metastatic melanoma. The diagnosis of metastatic melanoma and positivity for gp100 will be confirmed by the Laboratory of Pathology of the the National Cancer Institute (NCI).
  2. Patients must be refractory to high dose aldesleukin treatment if they are medically eligible to receive it. Patients with noncutaneous melanoma are not required to be refractory to high dose aldesleukin.
  3. gp100:154-162 reactive peripheral blood lymphocytes derived from a

    leukapheresis.

  4. HLA-A*0201 positive.
  5. Greater than or equal to 18 years of age.
  6. Willing to practice birth control during treatment and for four months after receiving the preparative regimen.
  7. Life expectancy of greater than three months.
  8. Willing to sign a durable power of attorney.
  9. Able to understand and sign the Informed Consent Document.
  10. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1 for the high dose aldesleukin cohort or ECOG 0, 1 or 2 for the low dose aldesleukin cohort.
  11. Hematology:

    • Absolute neutrophil count greater than 1000/mm^3 without support of filgrastim
    • Normal white blood cell (WBC) (greater than 3000/mm^3).
    • Hemoglobin greater than 8.0 g/dl
    • Platelet count greater than 100,000/mm^3.
  12. Serology:

    • Seronegative for human immunodeficiency virus (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.)
    • Seronegative for hepatitis B or hepatitis C.
  13. Chemistry:

    • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than less 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 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.
  14. Negative pregnancy test in women of child bearing potential because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
  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). 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 in Section 2.1.1.
  16. Six weeks must have elapsed since prior cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) antibody therapy to allow antibody levels to decline.
  17. Patients who have previously received anti-CTLA4 antibody and experienced treatment 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 preparative chemotherapy on the fetus or infant.
  2. Systemic steroid therapy required.
  3. For patients receiving high dose IL-2 only: Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  5. 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.)
  6. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  7. The following patients will be excluded from the high-dose IL-2 arm (but will be eligible for the low-dose arm):

    1. History of coronary revascularization or ischemic symptoms
    2. Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
    3. Documented LVEF of less than or equal to 45% tested in patients with:

      • Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
      • Age greater than or equal to 60 years old
    4. Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:

      • A prolonged history of cigarette smoking (20 pk/yrs of smoking)
      • Symptoms of respiratory dysfunction
  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: NCT00665470

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

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Udai S. Kammula, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00665470     History of Changes
Other Study ID Numbers: 080104, 08-C-0104
Study First Received: April 23, 2008
Results First Received: December 12, 2012
Last Updated: January 23, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Malignant Melanoma
HLA-A2
Immunotherapy
Clinical Response
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
Aldesleukin
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014