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VACCINE THERAPY WITH TUMOR SPECIFIC MUTATED P53 OR RAS PEPTIDES ALONE OR IN COMBINATION WITH CELLULAR IMMUNOTHERAPY WITH PEPTIDE ACTIVATED LYMPHOCYTES (PAL CELLS) ALONG WITH SUBCUTANEOUS IL-2


Phase 2
18 Years
N/A
Not Enrolling
Both
Breast Cancer, Cervical Cancer, Colorectal Cancer, Lung Cancer, Ovarian Cancer, Pancreatic Cancer

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Trial Information

VACCINE THERAPY WITH TUMOR SPECIFIC MUTATED P53 OR RAS PEPTIDES ALONE OR IN COMBINATION WITH CELLULAR IMMUNOTHERAPY WITH PEPTIDE ACTIVATED LYMPHOCYTES (PAL CELLS) ALONG WITH SUBCUTANEOUS IL-2


OBJECTIVES: I. Determine whether endogenous cellular immunity to a particular tumor-specific
mutated p53 or ras protein is present in patients with tumors expressing mutant p53 or ras.
II. Determine whether vaccination with antigen-presenting cells pulsed in vitro with
synthetic peptide corresponding to the tumor's p53 or ras mutation in the presence of
sargramostim (GM-CSF) can induce or boost patient cellular immunity to the mutated peptide
in this patient population. III. Assess the type and characteristics of the cellular
immunity generated. IV. Determine whether in vivo-primed T-cells generated against the p53
or ras mutation, expanded in vitro with corresponding peptide, and infused with subcutaneous
interleukin-2 can enhance the activity of specific cytotoxic T-lymphocyte immune response
and/or tumor response in these patients.

OUTLINE: Patients are assigned to 1 of 2 treatment regimens. The first 5 patients accrued
are assigned to Regimen A. Three weeks after all 5 patients are enrolled, additional
patients are accrued and assigned to Regimen B. All patients undergo peptide
hypersensitivity testing with the peptide they will be treated with prior to each
vaccination. Regimen A: Two days prior to each vaccination, peripheral blood mononuclear
cells (PBMC) are harvested. PBMC are incubated for 48 hours with either patient-specific
mutant p53 or ras peptide fragments and sargramostim (GM-CSF). The antigen-presenting cells
(APC) are irradiated prior to use. APC are reinfused on day 0. Treatment repeats after 3
weeks and then every 6 weeks for a total of 4 vaccinations. Regimen B: Patients are
vaccinated with APC as in Regimen A. PBMC are harvested prior to the first APC vaccination
and 1 week after the second, third, and fourth APC vaccinations. PBMC are incubated for 7
days with either peptide the patient was vaccinated with (mutant p53 or ras peptide
fragments) and interleukin-2 (IL-2). The peptide-activated lymphocytes (PAL) are reinfused
over 1 hour 2 weeks after each APC vaccination. Patients receive IL-2 subcutaneously 5 days
a week for 2 weeks beginning 4 hours after each PAL infusion. Patients in both regimens with
stable or responding disease continue treatment every 6 weeks. Patients achieving complete
response continue treatment for up to 1 additional year. Patients are followed at 1 and 2
months.

PROJECTED ACCRUAL: A maximum of 70 patients (5 per Regimen A, 28-65 per Regimen B) will be
accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically diagnosed advanced cancer considered incurable by
standard therapies and expressing mutant p53 or ras, e.g.: Lung Pancreatic Breast Colon
Cervical Ovarian p53 or ras mutation by point mutation, insertion, or deletion in
protein-coding sequence Tumor tissue required for p53 or ras mutation determination
(paraffin block or fresh tissue) Availability of tumor tissue for cell line preparation
and of tumor or lymph node tissues for tumor-infiltrating lymphocyte expansion desired No
history of CNS metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy:
More than 3 months Hematopoietic: WBC at least 2,000/mm3 Lymphocyte count at least 800/mm3
Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL ALT no
greater than 4 times normal No hepatitis B or C Renal: Creatinine no greater than 2.0
mg/dL Cardiovascular: No myocardial infarction within 6 months No New York Heart
Association class III or IV heart disease Immunologic: HIV negative No autoimmune disease,
e.g.: Systemic lupus erythematosus Multiple sclerosis Ankylosing spondylitis Responsive to
skin antigens Other: No weight loss of greater than 20% in the last 6 months No active
infection requiring antibiotics No active second malignancy except basal cell skin cancer
or carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Fertile
patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy and
recovered Chemotherapy: At least 4 weeks since prior chemotherapy and recovered Endocrine
therapy: At least 4 weeks since prior steroids and recovered Radiotherapy: At least 4
weeks since prior radiotherapy and recovered Surgery: Not specified

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Samir N. Khleif, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

CDR0000064192

NCT ID:

NCT00019084

Start Date:

February 1996

Completion Date:

May 2003

Related Keywords:

  • Breast Cancer
  • Cervical Cancer
  • Colorectal Cancer
  • Lung Cancer
  • Ovarian Cancer
  • Pancreatic Cancer
  • stage IV colon cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • recurrent non-small cell lung cancer
  • stage II pancreatic cancer
  • stage III pancreatic cancer
  • recurrent pancreatic cancer
  • recurrent colon cancer
  • recurrent cervical cancer
  • stage IVB cervical cancer
  • stage IV ovarian epithelial cancer
  • recurrent ovarian epithelial cancer
  • extensive stage small cell lung cancer
  • recurrent small cell lung cancer
  • stage IV non-small cell lung cancer
  • stage IV pancreatic cancer
  • Breast Neoplasms
  • Uterine Cervical Neoplasms
  • Colorectal Neoplasms
  • Lung Neoplasms
  • Ovarian Neoplasms
  • Pancreatic Neoplasms

Name

Location

Medicine BranchBethesda, Maryland  20892