Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	any age	NCI	NCI-86-C-183E NCI-T86-0225N, T86-0225

Objectives

I.  Evaluate the toxicity and therapeutic efficacy of 
interleukin-2/cyclophosphamide in patients with advanced cancer.
II.  Evaluate the toxicity and therapeutic efficacy of infusing tumor 
infiltrating lymphocytes (TIL), when available from freshly resected tumor, 
into selected patients.
III.  Mark and follow the in vivo distribution and survival of TIL in order to 
gain knowledge that should assist in optimizing the use of autologous 
lymphocytes as immunotherapy vehicles.
IV.  Evaluate the feasibility and safety of retroviral-mediated gene transfer 
using a marker gene in order to gain knowledge that should assist in 
augmenting TIL immunotherapy by the introduction of therapeutic genes.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Cancer patients of any age with 
evaluable metastasis who have failed standard treatment; as of May 1989, the 
first 10 patients entered will have metastatic melanoma, and thereafter, 
patients with renal cell and colorectal cancers will be given preference.  
Evidence of metastatic CNS disease excludes.  Patients must not have undergone 
any other form of cancer therapy in the month prior to study entry; patients 
requiring steroid therapy are not eligible.  An expected survival of more than 
2 months is required.  Patients with a history of coronary artery disease, 
cardiac arrhythmias that require treatment, evidence of a prior myocardial 
infarction on EKG, a history of congestive heart failure or angina pectoris 
requiring antianginal therapy, or over 50 years of age with poor performance 
on cardiac stress test are ineligible.  Active systemic infections (including 
a positive blood test for HIV antibodies), coagulation disorders, or other 
major medical illnesses of the cardiovascular or respiratory systems exclude.

Expected Enrollment

At least 2 patients will be treated at each dose level until the MTDs are 
defined; 50 patients will then be treated at the MTDs.

Outline

Nonrandomized study.  Two-patient cohorts are alternately entered on Regimens 
A and B, beginning with Regimen A.  Once a dose of CY/IL-2 has been 
established as tolerable on Regimen A or B, patients with available tumor 
infiltrating lymphocytes cultured from freshly resected tumor may be treated 
on Regimen C.  Selected patients on Regimen C who have tumor easily available 
for biopsy receive TIL containing a selectable marker gene.  Patients may also 
be treated on Regimen D or E.
Regimen A:  Biological Response Modifier Therapy. Interleukin-2 (Cetus), IL-2, 
NSC-373364; Cyclophosphamide, CY, NSC-26271.
Regimen B:  Biological Response Modifier Therapy.  IL-2; CY.  Altered starting 
dose of CY.
Regimen C:  Biological Response Modifier Therapy.  IL-2; CY; plus tumor 
infiltrating lymphocytes, TIL, incubated in vitro with IL-2 and in some cases 
with Interleukin-4, IL-4, NSC-620211.  Selected patients receive TIL 
containing a selectable marker gene.
Regimen D:  Biological Response Modifier Therapy.  IL-2; CY; TIL; plus 
alpha-Interferon, alpha-IFN.
Regimen E:  Biological Response Modifier Therapy.  IL-2; with or without CY; 
TIL; alpha-IFN.  Altered incubation process to increase TIL yield.

Rosenberg SA, Packard BS, Aebersold PM, et al.: Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 319 (25): 1676-80, 1988.[PUBMED Abstract]

Rosenberg SA, Lotze MT, Yang JC, et al.: Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg 210 (4): 474-84; discussion 484-5, 1989.[PUBMED Abstract]

Topalian SL, Solomon D, Avis FP, et al.: Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol 6 (5): 839-53, 1988.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Steven Rosenberg, MD, PhD, Protocol chair		Ph: 866-820-4505 Email: sar@nih.gov