Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors

Overview

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of cyclophosphamide when given together with combination chemotherapy and a peripheral stem cell transplant in treating patients with malignant solid tumors.

OBJECTIVES: * Determine whether autologous transplantation of mobilized CD34+ peripheral blood stem cells (PBSC) can provide complete hematologic reconstitution after myeloablative chemotherapy comprising etoposide (VP-16) and carboplatin (CBDCA) in patients with metastatic or recurrent rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma/primitive neuroectodermal tumor, germ cell tumors, childhood brain tumors, or hepatoblastoma. * Determine the frequency and yield of CD34+ PBSC and granulocyte-macrophage colony-forming units (GM-CFU) that are mobilized, harvested, and purified after a single priming course of high-dose cyclophosphamide (CTX) followed by filgrastim (G-CSF). * Correlate the number of CD34+ cells and GM-CFU in the autologous PBSC graft with time to engraftment of white blood cells, neutrophils, and platelets in these patients. * Determine the optimal day of PBSC harvest after a single priming course of high-dose CTX and G-CSF in these patients. * Determine whether CD34+ PBSC rescue and daily post-transplantation G-CSF decrease the time to hematopoietic recovery after high-dose VP-16 and CBDCA compared to historical results achieved in similar patients rescued with bone marrow. * Compare the tumor cell content of marrow, mobilized blood, and purified CD34+ PBSC graft preparations. * Determine the optimal timing of PBSC mobilization and harvest in relation to extent of prior chemotherapy in these patients. * Determine the feasibility of a single leukapheresis for PBSC harvest in children. * Determine the toxic effects of this regimen in these patients. * Determine the antitumor activity of this regimen in these patients. OUTLINE: This is a dose-escalation study of cyclophosphamide. Mobilization/harvest: Patients receive cyclophosphamide IV over 90 minutes on day 0 and filgrastim (G-CSF) subcutaneously or IV over 30 minutes on days 2-15 or until blood counts recover. Peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells on day 15. Bone marrow is also harvested in case insufficient PBSC are harvested. Preparative regimen/transplantation: Patients receive carboplatin IV over 1 hour and etoposide IV continuously on days -6 to -4. Cyclophosphamide is administered IV over 1 hour on days -3 and -2 or IV continuously on days -3 and -2, -4 to -2, -5 to -2, or -6 to -2. PBSC or bone marrow is reinfused on day 0. Cohorts of 3-10 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the highest dose at which 20% of patients experience dose-limiting toxicity. At least 6 additional patients receive cyclophosphamide at the MTD. PROJECTED ACCRUAL: A minimum of 36 patients will be accrued for this study.