Radiation, Chemotherapy, Vaccine and Anti-MART-1 and Anti-gp100 Cells for Patients With Metastatic Melanoma

Plain-language summary

This study evaluated radiotherapy, chemotherapy, a vaccine, and genetically modified immune cells (anti-MART-1 and anti-gp100 cells) together in patients with metastatic melanoma. It was open to patients aged 18 and older with measurable disease who had previously received aldesleukin (IL-2) without a lasting response and who were HLA-A*0201 positive. Run by the National Cancer Institute (NCI), the study was conducted in Phase 2 and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 2

Status

Completed

Sponsor

National Cancer Institute (NCI)

Intervention

MART-1: 26-35(27L) Peptide, Montanide ISA 51 VG, gp100:154-162 Peptide, Radiation, Aldesleukin, Fludarabine, Cyclophosphamide, Anti-gp 100:154 TCR PBL, Anti-MART-1 F5 TCR PBL

Start date

12/1/2008

Estimated completion

8/1/2011

Countries

United States

Related genes

Locations

• Bethesda, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

* INCLUSION CRITERIA:

  1. Metastatic melanoma with measurable disease.
  2. Previously received aldesleukin (IL-2) and have been either non-responders (progressive disease) or have recurred.
  3. Positive for gp100 and melanoma antigen recognized by T-cells (MART-1) (at least 1 plus and greater than 5 percent) as assessed by immunohistochemistry (IHC) in the Clinical Laboratory Improvement Amendments (CLIA) approved test in the Laboratory of Pathology, Center for cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH).
  4. Greater than or equal to 18 years of age.
  5. Willing to sign a durable power of attorney.
  6. Able to understand and sign the Informed Consent Document.
  7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
  8. Life expectancy of greater than three months.
  9. 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.
  10. Must be human leukocyte antigens (HLA-A\*0201) positive
  11. Serology:

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  1. 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.)
  2. Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.

  l. Hematology:
  1. Absolute neutrophil count greater than 1000/m\^3
  2. White blood cell (WBC) (greater than 3000/mm\^3.
  3. Platelet count greater than 100,000/mm\^3.
  4. Hemoglobin greater than 8.0 g/dl.

  m. Chemistry
  1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than 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.

  n. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

  o. 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).

  p. Six weeks must have elapsed since prior anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibody therapy to allow antibody levels to decline, and patients who have previously received anti-CTLA4 antibody 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. Systemic steroid therapy.
5. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
6. History of coronary revascularization
7. Documented left ventricular ejection fraction (LVEF) of less than 45 percent in patients with:

a) Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, 2 degree or 3 degree heart block

b) Age greater than or equal to 60 years old

h. Documented forced expiratory volume 1 (FEV1) less than or equal to 60 percent predicted for patients with:

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