Anti-gp100 Cells Plus ALVAC gp100 Vaccine to Treat Advanced Melanoma

This study has been terminated.
(The study was terminated due to low accrual.)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00610311
First received: February 6, 2008
Last updated: October 18, 2012
Last verified: October 2012
  Purpose

Background:

  • gp100 is a protein that is often found in melanoma tumors.
  • An experimental procedure developed for treating patients with melanoma uses anti-gp100 cells designed to destroy their tumors. The anti-gp100 cells are created in the laboratory using the patient's own tumor cells or blood cells.
  • The treatment procedure also uses a vaccine called plaque purified canarypox vector (ALVAC) gp100, made from a virus that ordinarily infects canaries and is modified to carry a copy of the gp100 gene. The virus cannot reproduce in mammals, so it cannot cause disease in humans. When the vaccine is injected into a patient, it stimulates cells in the immune system that may increase the efficiency of the anti gp 100 cells.

Objectives:

-To evaluate the safety and effectiveness of anti-gp100 cells and the ALVAC gp100 vaccine in treating patients with advanced melanoma.

Eligibility:

-Patients with metastatic melanoma for whom standard treatments have not been effective.

Design:

  • Patients undergo scans, x-rays and other tests and leukapheresis to obtain white cells for laboratory treatment.
  • Patients have 7 days of chemotherapy to prepare the immune system for receiving the gp100 cells.
  • Patients receive the ALVAC vaccine, anti-gp100 cells and interleukin-2 (IL-2) (an approved treatment for advanced melanoma). The anti gp100 cells are given as an infusion through a vein. The vaccine is given as injections just before the infusion of gp100 cells and again 2 weeks later. IL-2 is given as a 15-minute infusion every 8 hours for up to 5 days after the cell infusion for a maximum of 15 doses.
  • After hospital discharge, patients return to the clinic for periodic follow-up with a physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.

Condition Intervention Phase
Metastatic Melanoma
Skin Cancer
Drug: cyclophosphamide
Drug: fludarabine phosphate
Biological: Aldesleukin
Biological: ALVAC gp100 Vaccine
Biological: anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Anti-gp100:154-162 TCR-Gene Engineered Lymphocytes and ALVAC Virus Immunization

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants With Metastatic Melanoma Who Develop Clinical Tumor Regression (CR or PR) [ Time Frame: 4-6 weeks after treatment and then monthly for approximately 3 to 4 months or until off study criteria are met ] [ Designated as safety issue: No ]
    Clinical tumor response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 criteria. Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is a 30% decrease in lesions taking as reference the baseline sum longest diameter (LD). For details about the RECIST criteria see the protocol link module.


Secondary Outcome Measures:
  • Number of Participants With in Vivo Survival of T-cell Receptor (TCR) Gene-engineered Cells. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    T cell receptor (TCR) and vector presence will be quantitated in peripheral blood mononuclear cells (PBMC) samples using established polymerase chain reaction (PCR) techniques. This will provide data to estimate the in vivo survival of lymphocytes derived from the infused cells.

  • Number of Participants With Adverse Events [ Time Frame: 18.5 months ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

  • Number of Participants Who Develop Anti-mouse T Cell Receptor (TCR) Antibodies [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Blood samples are collected from the patient and an immunological test is conducted in the laboratory to determine if the patient has generated antibodies against the mouse T-cell receptor which is part of the anti-gp100 cells.


Enrollment: 3
Study Start Date: January 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2

ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 cell culture infectious dose 50% (CCID50) (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14.

Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)- 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)

Drug: cyclophosphamide
60 mg/kg day x 2 days intravenous in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg day x 2 days over 1 hour
Other Name: Cytoxan
Drug: fludarabine phosphate
25 mg/m^2 day intravenous piggy back over 30 minutes for 5 days
Other Name: Fludara
Biological: Aldesleukin
720,000 IU/kg intravenously over 15 minutes every 8 hours (+/- 1 hour) for up to 5 days.
Other Name: Proleukin
Biological: ALVAC gp100 Vaccine
0.5 ml containing a target dose of 10^7 CCID50 (with a range of approximately 10^6,4 to 10^7,9/mL) of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL)
Other Name: ALVAC
Biological: anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL)
3 x 10^11 anti-gp100:154-162 TCR engineered PBL by intravenous infusion. A minimum of approximately 5 x 10^8 cells will be given.

  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. Metastatic melanoma with measurable disease.
  2. Previously received high dose interleukin-2 (IL-2) and have been either non-responders (progressive disease) or have recurred.
  3. Positive for gp100 by immunohistochemistry (IHC) which will be reviewed by the Laboratory of Pathology at National Cancer Institute (NCI).
  4. Tumor infiltrating lymphocyte (TIL) cells not available for treatment on other Surgery Branch protocols.
  5. Greater than or equal to 18 years of age.
  6. Willing to sign a durable power of attorney.
  7. Able to understand and sign the Informed Consent Document.
  8. Clinical performance status of Eastern Oncology Oncology Group (ECOG) 0 or 1.
  9. Life expectancy of greater than three months.
  10. Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.
  11. Must be human leukocyte antigens (HLA-A) 0201 positive.
  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 antigen and hepatitis C antibody unless antigen negative.
  13. Hematology:

    • Absolute neutrophil count greater than 1000/mm^3.
    • White blood cell (WBC) (greater than 3000/mm^3).
    • Platelet count greater than 100,000/mm^3.
    • Hemoglobin greater than 8.0 g/dl.
  14. Chemistry

    • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
  15. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
  16. 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).
  17. Six weeks must have elapsed since prior MDX-010 therapy to allow antibody levels to decline, and patients who have previously received MDX-010 or ticilimumab 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. 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. Ongoing 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. Systemic steroid therapy.
  6. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  7. History of coronary revascularization.
  8. Documented left ventricular ejection fraction (LVEF) of less than 45 percent in patients with:

    • Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, 2 degree or 3 degree heart block.
    • Age greater than or equal to 60 years old.
  9. Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60 percent predicted for patients with:

    • A prolonged history of cigarette smoking (greater than 20 pack/year within the past 2 years).
    • Symptoms of respiratory distress.
  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: NCT00610311

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, National Institutes of Health
  More Information

Additional Information:
Publications:
Responsible Party: Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00610311     History of Changes
Other Study ID Numbers: 080055, 08-C-0055
Study First Received: February 6, 2008
Results First Received: March 14, 2012
Last Updated: October 18, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Metastatic Melanoma
Immunotherapy
Vaccination
Tumor Regression
Skin Cancer

Additional relevant MeSH terms:
Skin Neoplasms
Melanoma
Neoplasms by Site
Neoplasms
Skin Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Vidarabine
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
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on August 27, 2014