NCT00096382

Cyclophosphamide, Fludarabine, and Total-Body Irradiation Followed By Cellular Adoptive Immunotherapy, Autologous Stem Cell Transplantation, and Interleukin-2 in Treating Patients With Metastatic Melanoma

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: National Institutes of Health Clinical Center (CC) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Biological therapies, such as cellular adoptive immunotherapy, work in different ways to stimulate the immune system and stop tumor cells from growing. Autologous stem cell transplant may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Interleukin-2 may stimulate a person's lymphocytes to kill tumor cells. Combining chemotherapy, radiation therapy, and biological therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with radiation therapy followed by cellular adoptive immunotherapy, autologous stem cell transplant, and interleukin-2 works in treating patients with metastatic melanoma.

Detailed description

OBJECTIVES: Primary * 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. Secondary * 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 regimen. OUTLINE: * 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.

Conditions

• Melanoma (Skin)

Interventions

Type	Name	Description
BIOLOGICAL	aldesleukin	high dose: 720,000 IU/kg intravenously over 15 minutes every 8 hours for up to 5 days (maximum 5 doses) or low dose: 250,000 IU/kg subcutaneously daily for 5 days, after a two day rest, 125,000 IU/kg subcutaneously daily for 5 days for five weeks (2 days rest per week)
BIOLOGICAL	filgrastim	10 mcg/kg/day daily subcutaneously until neutrophil count \>1x10\^9/1.
BIOLOGICAL	therapeutic tumor infiltrating lymphocytes	Lymphocytes that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
DRUG	cyclophosphamide	60 mg/kg/day x 2 days intravenously over 1 hour
DRUG	fludarabine phosphate	25 mg/m\^2/day intravenous piggyback daily over 15-20 minutes for 5 days
RADIATION	radiation therapy	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.

Timeline

• Start date: 2004-09-01
• Primary completion: 2009-01-01
• Completion: 2009-01-01
• First posted: 2004-11-09
• Last updated: 2015-10-28
• Results posted: 2013-03-27

Locations

2 sites across 1 country: United States