Laboratory-Treated Autologous Lymphocytes and Aldesleukin After Cyclophosphamide and Fludarabine in Treating Patients With Metastatic Melanoma
|ClinicalTrials.gov Identifier: NCT00863330|
Recruitment Status : Terminated (administrative decision- PI retired and treating physician left the institution)
First Posted : March 18, 2009
Results First Posted : December 17, 2014
Last Update Posted : January 6, 2015
RATIONALE: Treating lymphocytes in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving laboratory-treated lymphocytes and aldesleukin together with cyclophosphamide and fludarabine may kill more tumor cells.
PURPOSE: This phase II trial is studying how well laboratory-treated autologous lymphocytes and aldesleukin work when given after cyclophosphamide and fludarabine in treating patients with metastatic melanoma.
|Condition or disease||Intervention/treatment||Phase|
|Melanoma (Skin)||Biological: Tumor Infiltrating Lymphocytes (TIL)||Phase 2|
- Determine the ability of treatment with short-term cultured autologous tumor-infiltrating lymphocytes (TIL) in combination with high-dose aldesleukin after a nonmyeloablative lymphocyte-depleting preparative regimen comprising cyclophosphamide and fludarabine phosphate to mediate tumor regression in patients with metastatic melanoma.
- Determine the toxicity of this treatment regimen.
- Determine the rate of repopulation of the young TIL cells.
- Establish in vitro immunological correlates that predict in vivo persistence and clinical response.
- Conditioning regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.
- Tumor-infiltrating lymphocyte (TIL) infusion and high-dose aldesleukin: Patients receive short-term cultured autologous TIL IV over 20-30 minutes on day 0. Patients also receive high-dose aldesleukin IV over 15 minutes every 8 hours on days 0-4.
Patients with stable disease, partial response, or recurrent disease after initial response may receive 1 additional course of treatment (as above) beginning 8 weeks after completion of aldesleukin.
Blood samples are collected at baseline, at 1 week and 1 month after TIL infusion, and then periodically thereafter for research studies. Samples are analyzed for differences in function and phenotype prior to and after TIL infusion. The immunological correlates of treatment are also evaluated using FACS, cytokine release assays, ELISPOT assays, flow cytometry, and PCR. TIL that are cryopreserved at the time of infusion are analyzed to determine cell phenotype and function; correlation of in vitro characteristics of the infused cells with in vivo antitumor activity; and the activity, specificity, and telomere length using flow FISH.
After completion of study treatment, patients are followed at 4-6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma|
|Study Start Date :||February 2009|
|Actual Primary Completion Date :||July 2012|
|Actual Study Completion Date :||July 2012|
|Experimental: Determine toxicity of treatment regimen.||
Biological: Tumor Infiltrating Lymphocytes (TIL)
Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.
- Primary Objective [ Time Frame: 4-6 weeks after completion of TIL ]Determine the ability of autologous cells infused with minimal in vitro culture in conjunction with high dose interleukin -2 (IL-2) following non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00863330
|United States, Wisconsin|
|Aurora St. Luke's Medical Center|
|Milwaukee, Wisconsin, United States, 53215|
|Principal Investigator:||John P. Hanson, MD||St. Luke's Medical Center|
|Principal Investigator:||Jonathan S. Treisman, MD||St. Luke's Medical Center|