Treatment of Patients With Metastatic Melanoma Using a Transplant of Autologous Lymphocytes Reactive With Tumor Following a Myeloablative Lymphocyte Depleting Regimen of Chemotherapy, Total Body Irradiation and Reconstitution With CD34+ Cells
- Determine complete clinical tumor regression in patients with metastatic melanoma
treated with a myeloablative lymphoid-depleting preparative regimen comprising
cyclophosphamide, fludarabine, and total body irradiation followed by autologous
tumor-reactive tumor-infiltrating lymphocyte infusion, autologous CD34+ stem cell
transplantation, and low-dose or high-dose interleukin-2.
- Evaluate the safety of this regimen in these patients.
- Determine the survival of the infused lymphocytes by analyzing the sequence of the
variable region of the T-cell receptor or flow cytometry in patients treated with this
- Autologous stem cell collection: Patients receive filgrastim (G-CSF) subcutaneously
(SC) twice daily for 8 days. Beginning on day 5 of G-CSF, patients undergo apheresis
daily for up to 3 days. Patients may receive 1 additional course of G-CSF and apheresis
or use stem cells stored from a prior stem cell harvest in order to obtain an adequate
number of cells.
- Lymphocyte-depleting myeloablative preparative regimen: Patients receive
cyclophosphamide intravenous (IV) over 1 hour on days -5 and -6 and fludarabine IV over
15-30 minutes on days -6 to -2. Patients also undergo total body irradiation on day -1.
- Autologous lymphocyte infusion: Patients receive autologous tumor-reactive
tumor-infiltrating lymphocytes IV over 20-30 minutes on day 0* followed by G-CSF SC
once daily until blood counts recover.
- Autologous stem cell transplantation: Patients receive autologous CD34+ stem cells IV
on day 2.
- Interleukin therapy: Patients are assigned to 1 of 2 cohorts, depending on whether they
have received prior high-dose interleukin-2 (IL-2).
- Cohort 1 (patients who received prior high-dose IL-2): Beginning on day 0*,
patients receive high-dose IL-2 IV over 15 minutes 3 times daily for up to 5 days
(maximum of 15 doses).
- Cohort 3 (patients who have not received prior high-dose IL-2): Patients receive
treatment as in cohort 1.
NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.
Patients are evaluated at 4-6 weeks.
PROJECTED ACCRUAL: A total of 116 patients will be accrued for this study.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical Tumor Regression
Tumor regression is defined as a complete response (CR) or partial response (PR) and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Every 4-6 weeks for up to 1 year, and then every 6 months for up to 5 years.
Steven A. Rosenberg, MD, PhD
NCI - Surgery Branch
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|
|NCI - Surgery Branch||Bethesda, Maryland 20892-1201|