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

NCT00610311 | Terminated Phase 2 Results DMC

• 2 other identifiers: 08005508-C-0055
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Melanoma; Skin Cancer

Keywords

Metastatic Melanoma; Immunotherapy; Vaccination; Tumor Regression; Skin Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Metastatic Melanoma Who Develop Clinical Tumor Regression (CR or PR)

  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.

  4-6 weeks after treatment and then monthly for approximately 3 to 4 months or until off study criteria are met

Secondary Outcomes (3)

• Number of Participants With in Vivo Survival of T-cell Receptor (TCR) Gene-engineered Cells.

  1 month

• Number of Participants With Adverse Events

  18.5 months

• Number of Participants Who Develop Anti-mouse T Cell Receptor (TCR) Antibodies

  1 month

Study Arms (1)

ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2

EXPERIMENTAL

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; Drug: fludarabine phosphate; Biological: Aldesleukin; Biological: ALVAC gp100 Vaccine; Biological: anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL)

Interventions

cyclophosphamide DRUG

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

Also known as: Cytoxan

ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2

fludarabine phosphate DRUG

25 mg/m\^2 day intravenous piggy back over 30 minutes for 5 days

Also known as: Fludara

ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2

Aldesleukin BIOLOGICAL

720,000 IU/kg intravenously over 15 minutes every 8 hours (+/- 1 hour) for up to 5 days.

Also known as: Proleukin

ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2

ALVAC gp100 Vaccine BIOLOGICAL

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)

Also known as: ALVAC

ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2

anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL) BIOLOGICAL

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.

ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.
• 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.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• 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).
• Systemic steroid therapy.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• History of coronary revascularization.
• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9. doi: 10.1073/pnas.91.9.3515.

  PMID: 8170938 BACKGROUND

• Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52. doi: 10.1084/jem.180.1.347.

  PMID: 7516411 BACKGROUND

• Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995 Oct 19;333(16):1038-44. doi: 10.1056/NEJM199510193331603.

  PMID: 7675046 BACKGROUND

Related Links

• Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

Cyclophosphamide; fludarabine phosphate; aldesleukin

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

Limitations and Caveats

Early termination leading to a small number of subjects analyzed.

Results Point of Contact

• Title: Steven A. Rosenberg, M.D.
• Organization: National Cancer Institute, National Institues of Health

sar@mail.nih.gov

301-496-4164

Study Officials

• Steven A Rosenberg, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2008
• First Posted: February 7, 2008
• Study Start: January 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: October 28, 2015
• Results First Posted: April 10, 2012

Record last verified: 2015-09

Locations

US (1)