Chemotherapy, Irradiation, Cell Infusions, and Interleukin-2 to Treat Metastatic Melanoma

Summary

Background:

* In a study in humans with melanoma, patients given total body irradiation to suppress the immune system in conjunction with chemotherapy showed a significant clinical response.
* In previous studies, about one-half of patients given tumor-fighting cells (cells created from the patient's tumor cells and grown in the laboratory) showed some anti-tumor response.

Objective: To determine whether tumor-fighting cells taken from a melanoma tumor and grown in the lab can more effectively at fight melanoma when the patient's immune system is suppressed and cannot attack them.

Eligibility: Patients 18 years of age or older with metastatic melanoma who have tumor reactive cells available.

Design:

-Patients are assigned to one of two groups - those having received prior therapy with Interleukin-2 (IL-2) and those who have not.

After five days of injections of filgrastim, a medicine to stimulated the growth of white blood cells, patients undergo apheresis or bone marrow harvesting, or both, to collect stem cells for later re-infusion. For apheresis, whole blood is collected through a needle in an arm vein and circulated through a cell-separating machine where the stem cells are extracted. The rest of the blood is returned through the same needle or a needle in the other arm. Bone marrow harvesting is done under general anesthesia. Stem cells are collected through a large needle inserted into the hipbone.-Patients' immune system cells and bone marrow function are eliminated with chemotherapy (7 days) and total body irradiation (3 days) so the patient's immune system cells will not fight the tumor-fighting cells they are given in treatment.

* 1 to 3 days after total body irradiation, patients receive the tumor-fighting cells by intravenous (IV) infusion. After the cells are infused, they receive interleukin-2 (IL-2) infusions every 8 hours for 5 days.
* 2 days after infusion of the tumor-fighting cells, patients receive the stem cells collected earlier by apheresis.
* Patients are evaluated 4 to 6 weeks after cell infusion to look for tumor response to treatment. Patients whose tumor has not grown return to the National Institutes of Health (NIH) every 1 to 3 months for blood tests, scans and x-rays.

Conditions

• Metastatic Melanoma

Interventions

BIOLOGICAL

Melanoma Reactive TIL

DRUG

Cyclophosphamide

60 mg/kg/ day x 2 days intravenous

BIOLOGICAL

IL-2

720,000 IU/kg/dose every 8 hours for up to 15 doses

DRUG

Fludarabine

25 mg/m\^2/day intravenous x 5 days

RADIATION

1200 total body irradiation (TBI)

1200 cGY total body radiation

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven A Rosenberg, M.D. · National Cancer Institute, National Institutes of Health

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-04-30

Primary Completion

2009-02-28

Completion

2009-03-31

Countries

• United States

Study Locations