Study of Gene Modified Immune Cells in Patients With Advanced Melanoma (F5)
The purpose of this phase 2 study is to find the best way to give this new experimental regimen and determine if it can treat metastatic melanoma in humans. In this phase 2 study, the experimental products are given initially to a group of 8 people. If safe and found to have significant anti-tumor activity, it will be given to up to 14 other people, for a total of 22 people in this study. Physicians watch subjects carefully for any harmful side effects. Although the experimental regimen has been well tested in laboratory and animal studies, and a similar regimen has been given to a group of patients at the National Cancer Institute in Bethesda, MD, the side effects in people cannot be completely known ahead of time. This protocol is offered only to people whose condition cannot be helped by other known treatments.
The study procedures will start with the collection of white blood cells through apheresis (a procedure in which blood is drawn from a patient and separated into its components, some of which are retained, such as white blood cells, and the remainder returned by transfusion to the patient).
Subjects will be asked to undergo two aphereses, one to make the gene-modified MART-1 TCR CTLs and the dendritic cell vaccines, and a second one after the subject receives the gene modified cells to later study them in the blood.
On the day of the first apheresis, subjects will be admitted to the hospital and will receive chemotherapy over the next five days which decreases the risk of rejection of the transferred cells by the subject's immune system and facilitates their expansion and attack of the melanoma lesions. During this time, the gene-modified MART-1 TCR CTLs and the dendritic cells will be manufactured in the laboratory from the apheresis product and will be extensively tested to assure that they express the appropriate TCR and that they do not contain any contaminating bacteria or virus. Then the gene-modified MART-1 TCR CTLs will be given back to the subject through a vein in the arm. It will be followed by vaccination with the dendritic cells under the skin. During the next fourteen days, subjects will also receive interleukin 2 (IL-2), which is a standard treatment for patients with metastatic melanoma. During the next 2 to 3 weeks, subjects will stay in the hospital until the study investigators determine that the subject has fully recovered from all of the procedures, and it is safe for the subject to go home. Chemotherapy frequently causes a decrease in the platelet or red blood cells, and therefore subjects may require platelet and/or red blood cell transfusions.
|Metastatic Melanoma||Biological: F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cells Drug: non-myeloablative conditioning chemotherapy||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Adoptive Transfer of MART-1 F5 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) After a Nonmyeloablative Conditioning Regimen, With Administration of MART-126•35-Pulsed Dendritic Cells and Interleukin-2, in Patients With Advanced Melanoma|
- Response rate: The two-stage phase II study design includes response rate by RECIST criteria as the primary endpoint. [ Time Frame: 3 months ]
- Other key measures that will be used to evaluate the intervention(s) or, for observational studies, that are a focus of the study. [ Time Frame: 3 months ]Within the first 8 patients in the two-stage phase II design, an assessment of safety (less than 33% dose limiting toxicities) and feasibility (adequate cell therapy manufacture) will be made.
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: F5 TCR transgenic cells
F5 TCR transgenic cell adoptive transfer therapy
Biological: F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cells
After chemotherapy, patients receive up to 1 x 10(9) MART-1 F5 TCR transgenic T cells infused i.v., 1 x 10(7) MART-1 peptide pulsed dendritic cells intradermally, and low dose IL-2 500,000 IU/m2 s.c. twice daily for 14 days.
Other Names:Drug: non-myeloablative conditioning chemotherapy
Patients receive non-myeloablative conditioning chemotherapy with Cyclophosphamide 60 mg/kg/day x 2 days and Fludarabine 25 mg/m2/day i.v. over 30 minutes for 4 days
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00910650
|Contact: Antoni Ribas, MDemail@example.com|
|Contact: Elizabeth Sejafirstname.lastname@example.org|
|United States, California|
|University of California Los Angeles, David Geffen School of Medicine||Recruiting|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||Antoni Ribas, MD||University of California, Los Angeles|
|Principal Investigator:||Bartosz Chmielowski, MD, PhD||University of California, Los Angeles|
|Principal Investigator:||James S Economou, MD, PhD||University of California, Los Angeles|
|Principal Investigator:||John A Glaspy, MD, MPH||University of California, Los Angeles|