Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy and Biological Therapy in Treating Patients With Advanced Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI NCI-95-C-0105A NCI-T94-0096N, T94-0096, NCT00019084

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.

Entry 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

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

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Samir N. Khleif, MD, Protocol chair		Ph: 301-435-5392 Email: khleif@nih.gov

Registry Information
Official Title		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
Trial Start Date		1996-02-22
Registered in ClinicalTrials.gov		NCT00019084
Date Submitted to PDQ		1996-02-22
Information Last Verified		2007-04-20