Prospective Randomized Comparative Study of Cell Transfer Therapy Using CD8+-Enriched Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Compared to High-Dose Aldesleukin in M...

Summary

Background:

\- Adoptive cell therapy involves taking white blood cells called lymphocytes from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient to allow the cells to attack the tumor. Because this process is lengthy and difficult to perform, researchers have been developing improved means of performing adoptive cell therapy. Researchers are now interested in comparing adoptive cell therapy with the standard treatment for metastatic melanoma (skin cancer).

Objectives:

\- To compare the effectiveness of adoptive cell therapy with standard high-dose aldesleukin as a treatment for metastatic melanoma.

Eligibility:

* Individuals 18 years of age or older who have been diagnosed with metastatic melanoma and have not previously received aldesleukin therapy or cell therapy for their disease.
* Participants must have at least one tumor that can be easily removed as part of the treatment procedure.

Design:

* Participants will be screened with a full medical history, physical examination, blood and urine tests, and imaging scans to evaluate tumor size and treatment options.
* Participants will be separated into two groups, in which one group will have adoptive cell therapy and one will have aldesleukin treatment.
* Adoptive Cell Therapy

* Participants will have a tumor sample taken in order to collect white blood cells for treatment. Participants whose tumors do not provide sufficient white blood cells may be switched to the aldesleukin-only treatment group.
* The white blood cells will be grown in the laboratory for several weeks.
* Prior to receiving cell therapy, participants will receive chemotherapy for 7 days to improve the chances of successful treatment.
* Participants will have cell therapy followed by high-dose aldesleukin treatment every 8 hours for up to 5 days. This treatment will be followed by 1 to 2 weeks of recovery time as an inpatient at the clinical center.
* Participants will be evaluated at 12 weeks following the start of the study, every 2 to 3 months for the first year, every 6 months for the next 5years, and then yearly thereafter..
* Standard Aldesleukin Treatment

* Participants will have high-dose aldesleukin treatment every 8 hours for up to 5 days (one cycle of treatment), and will have a second cycle of treatment 7 to 10 days after the first cycle.
* If tests show that the tumors have grown, participants will be offered the chance to have additional cycles of aldesleukin, or begin a cell therapy treatment.
* Participants will be evaluated at 12 weeks following the start of the study, every 2 to 3 months for the first year, every 6 months for the next 5years, and then yearly thereafter.

Conditions

• Skin Cancer
• Melanoma
• Metastatic Melanoma

Interventions

BIOLOGICAL

Aldesleukin

Aldesleukin 720,000 IU/kg IV over 15 minute every eight hours and continuing for up to 5 days (maximum of 15 doses). Patients will receive one additional cycle of aldesleukin approximately 10-14 days after completion of the first cycle of aldesleukin.

BIOLOGICAL

CD8 enriched Young TIL

Adoptive Cell Therapy consisting of the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of between 1x10\^9 to 2x10\^11 CD8+ enriched tumor infiltrating lymphocytes (minimum of 5 x 10\^8) and the administration of high-dose aldesleukin.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Ramaprasad Srinivasan, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-04-30

Primary Completion

2012-04-30

Completion

2012-04-30

Countries

• United States

Study Locations