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Phase II Study of Metastatic Cancer That Overexpresses P53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-P53 TCR-Gene Engineered Lymphocytes

NCT00393029 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 12

Last updated 2011-08-15

Study results available
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Summary

Background:

The p53 gene normally suppresses tumor growth, but when it is mutated, or damaged, tumors can grow unchecked.

In cancers where the p53 gene has mutated, an increased level of p53(overexpression of p53) can be measured in the tumor.

Objectives To determine whether advanced cancers that overexpress p53 can be treated effectively with lymphocytes (white blood cells) that have been genetically engineered to contain an anti-p53 protein.

Eligibility Patients 18 years of age and older with metastatic cancer (cancer that has spread beyond the original site) Patient's tumor overexpresses p53 Patient's leukocyte antigen type is HLA-A 0201 Design

Patients undergo the following procedures:

Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the anti-p53 protein is inserted into the cells using an inactivated (harmless)virus in a process called transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effectiveness of the study treatment.

Chemotherapy. Patients are given chemotherapy through a vein (intravenously, IV) for 1 week to suppress the immune system so that the patients immune cells do not interfere with the treatment.

Treatment with anti-p53 cells. Patients receive an IV infusion of the transduced cells containing anti-p53 protein, followed by infusions of a drug called IL-2, which helps boost the effectiveness of the transduced white cells.

Patients may undergo a tumor biopsy (removal of a small piece of tumor tissue). Patients are evaluated with laboratory tests and imaging tests, such as computed tomography (CT) scans 4 to 6 weeks after treatment and then once a month 3 to 4 months to determine the response to treatment.

Patients have blood tests at 1, 3, 6 and 12 months and then annually for the next 10 years.

Conditions

  • Anti-p53 TCR-Gene

Interventions

BIOLOGICAL

anti-protein 53 or tumor protein 53 (p53) T-cell receptor transduced peripheral blood lymphocytes

Peripheral blood lymphocytes are harvested by lymphapheresis and engineered to express a T cell receptor that binds to P53.

BIOLOGICAL

aldesleukin

720,000 IU/kg intravenously over 15 minutes every 8 hours for up to 5 days

BIOLOGICAL

filgrastim

Beginning on day 1 or 2, administered subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day); continue daily until neutrophil count \> 1.0 x 10\^9/L x 3 days or \> 5.0 x 10\^9/L.

DRUG

cyclophosphamide

60 mg/kg/day x 2 days intravenously in 250ml dextrose 5% in water (D5W) with mesna 15 mg/kg/day x 2 days over 1 hour.

DRUG

fludarabine phosphate

25 mg/m2/day intravenously piggyback (IVPB) daily over 30 minutes for 5 days.

Sponsors & Collaborators

  • National Cancer Institute (NCI)

    lead NIH

Principal Investigators

  • Steven A Rosenberg, M.D., Ph.D · NCI, NIH

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2006-10-31
Primary Completion
2008-11-30
Completion
2008-11-30

Countries

  • United States

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00393029 on ClinicalTrials.gov