Anti-MART-1 F5 Cells Plus ALVAC MART-1 Vaccine to Treat Advanced Melanoma

NCT00612222 | Terminated Phase 2 Results DMC

• 2 other identifiers: 08005608-C-0056
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Melanoma antigen recognized by T-cells (MART)-1 is a protein present in melanoma cells.
• An experimental procedure developed for treating patients with melanoma uses the anti-MART-1 F5 gene and a type of virus to make special cells called anti-MART-1 F5 cells that are designed to destroy the patient's tumor. These 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) MART-1, made from a virus that ordinarily infects canaries and is modified to carry a copy of the MART-1 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-MART-1 F5 cells. Objectives:
• To evaluate the safety and effectiveness of anti-MART-1 F5 and the ALVAC vaccine in treating patients with advanced melanoma. Eligibility:
• Patients 18 years of age 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 anti-MART-1 F5.
• Patients receive the ALVAC vaccine, anti-MART-1 F5 cells and interleukin-2 (IL-2) (an approved treatment for advanced melanoma). The anti-MART-1 F5 cells are given as an infusion through a vein. The vaccine is given as injections just before the infusion of anti-MART-1 F5 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

Immunotherapy; Metastatic Melanoma; 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 (2)

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

  1 month

• Number of Participants With Adverse Events

  15 months

Study Arms (1)

ALVAC plus anti-MART-1 F5 TCR PBL + HD IL-2

EXPERIMENTAL

ALVAC plus anti-MART-1 F5 T cell receptor (TCR ) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin 2 (IL-2): ALVAC vaccine-approximately 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 10\^7,9/mL) of the MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10\^7 CCID50/2 mL). This will be repeated on day 14. Aldesleukin - 720,000 IU/kg intravenously over 15 minutes every 8 hours (+/- 1 hour) for up to 5 days.

Biological: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes; Biological: ALVAC MART-1 Vaccine; Biological: aldesleukin; Drug: cyclophosphamide; Drug: fludarabine phosphate

Interventions

autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes BIOLOGICAL

ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 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 MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10\^7 CCID50/2 mL). This will be repeated on day 14.

ALVAC plus anti-MART-1 F5 TCR PBL + HD IL-2

ALVAC MART-1 Vaccine BIOLOGICAL

ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 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 MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10\^7 CCID50/2 mL). This will be repeated on day 14.

ALVAC plus anti-MART-1 F5 TCR PBL + HD IL-2

aldesleukin BIOLOGICAL

Aldesleukin - 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)

Also known as: IL2, Proleukin, Recombinant human interleukin 2

ALVAC plus anti-MART-1 F5 TCR PBL + HD IL-2

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-MART-1 F5 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-MART-1 F5 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 MART-1 by immunohistochemistry (IHC) which will be reviewed by the Laboratory of Pathology at National Cancer Institute (NCI).
• Tumor infiltrating lymphocytes (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 Cooperative 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.
• Patients 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 or ischemic symptoms.
• Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45 percent.
• Documented LVEF of less than or equal to 45 percent 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.
• Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60 percent predicted tested in patients with:
• A prolonged history of cigarette smoking (20 pk/yrs of smoking).
• Symptoms of respiratory dysfunction.

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

• 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

• 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

Related Links

• Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

aldesleukin; Interleukin-2; Cyclophosphamide; fludarabine phosphate

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)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Steven A. Rosenberg, M.D.
• Organization: National Cancer Institute (NCI), National Institutes of Health (NIH)

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 8, 2008
• First Posted: February 11, 2008
• Study Start: January 1, 2008
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: October 28, 2015
• Results First Posted: April 19, 2012

Record last verified: 2015-10

Locations

US (1)