Trial Information

TREATMENT OF CHILDREN AND YOUNG ADULTS WITH RECURRENT/REFRACTORY SOLID TUMORS WITH HIGH DOSE ETOPOSIDE AND CARBOPLATIN PLUS ESCALATING DOSE CYCLOPHOSPHAMIDE, FOLLOWED BY HEMATOPOIETIC RESCUE USING AUTOLOGOUS CD34+ SELECTED BLOOD STEM CELLS: A PILOT STUDY

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.