Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor

OBJECTIVES:

I. To assess the feasibility of a novel combination conditioning therapy with
busulfan/melphalan and topotecan followed by autologous hematopoietic stem cell
transplantation (HSCT) in patients with relapsed, refractory and/or poor risk pediatric solid
tumors.

II. To determine within the confines of this pilot study, myeloid and platelet engraftment,
overall survival and disease-free survival in patients with relapsed, refractory pediatric
solid tumors and in patients who have solid tumors with poor risk factors at the time of
diagnosis.

III. To determine the pharmacokinetics of topotecan.

OUTLINE:

AUTOLOGOUS HEMATOPOIETIC STEM CELL OR AUTOLOGOUS BONE MARROW COLLECTION: Patients undergo
stem cell mobilization per institutional guidelines with G-CSF IV or subcutaneously,
continuing until the completion of leukapheresis. Patients undergo apheresis after
mobilization and continue until a minimum of 2.0 x 10^6 CD34 cells/kg or more are collected.
Cells are processed and cryopreserved following institutional guidelines. Patients who
collect > 2.0 x 10^6 CD34+ cells/kg may proceed to high-dose chemotherapy.

HIGH-DOSE CHEMOTHERAPY: Patients receive topotecan hydrochloride IV continuously over 24
hours on days -8 to -4, busulfan IV every 6 hours on days -8 to -4, and melphalan IV over 30
minutes on days -3 and -2.

AUTOLOGOUS HEMATOPOIETIC STEM CELL OR AUTOLOGOUS BONE MARROW REINFUSION: Patients undergo
autologous hematopoietic stem cell transplantation or autologous bone marrow transplantation
on day 0. Patients also receive G-CSF IV daily beginning on day +5 and continuing until blood
counts recover.

After completion of study treatment, patients are followed every 3 months for 1 year and then
annually thereafter.

Inclusion

- Patients with relapsed neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, PNET, brain
tumors, soft tissue sarcomas, Wilm's tumors, germ cell tumors or other solid tumors
who achieved at least partial response (PR) to chemotherapy, surgery, or radiotherapy

- Newly diagnosed patients for poor-risk pediatric solid tumors: metastatic Ewing's,
metastatic PNET, rhabdomyosarcoma, soft tissue sarcomas, octeomesenchymoma, and others
that are at a high risk of relapse and who have achieved at least partial response
(PR) to chemotherapy, surgery, or radiotherapy

- For any of the above categories, an attempt to achieve a complete response (CR) or PR
should be made; pre-transplant modalities may include surgery, chemotherapy, or
radiation therapy; radiation must not include lung fields; only patients in CR or PR
at the primary site will be eligible

- HIGH-DOSE CHEMOTHERAPY: Histologically confirmed diagnosis by Anatomic Pathology
Department; if recurrent or metastatic disease, histologic confirmation should be
obtained, with the exception of brain stem tumors; in neuroblastoma, demonstration of
marrow metastases with elevated urinary catecholamines is adequate for diagnosis

- HIGH-DOSE CHEMOTHERAPY: No contraindications to the stem cell collection by apheresis
or by bone marrow harvesting

- HIGH-DOSE CHEMOTHERAPY: All patients, or their legal guardians must have signed a
voluntary informed consent in accordance with the institutional and federal guidelines

- HIGH-DOSE CHEMOTHERAPY: Adequate renal function as demonstrated by creatinine
clearance (12 or 24 hour urine collection) or glomerular filtration rate (GFR) > 60
ml/min/1.73m^2

- HIGH-DOSE CHEMOTHERAPY: Adequate cardiac function as demonstrated by ejection fraction
> 55% by echocardiogram or MUGA

- HIGH-DOSE CHEMOTHERAPY: Adequate hepatic function as demonstrated by bilirubin < 2
mg/dL, SGOT and SGPT < 5 x upper limits of normal

- HIGH-DOSE CHEMOTHERAPY: Adequate bone marrow function as evidenced by platelet count >
50,000/ul and absolute granulocyte count >= 750 ul

- HIGH-DOSE CHEMOTHERAPY: Adequate pulmonary function adults (older than 16 years): FEV1
> 2 liters, room air PaO2 > 70 mm Hg, room air PaCO2 < 42 mm Hg, and DLCO > 50%
predicted; children (younger than 16 years): DLCO > 50% predicted

- HIGH-DOSE CHEMOTHERAPY: Pretreatment tests and clinical and laboratory tests must have
been performed within 4 weeks prior to initiation of high-dose chemotherapy

- HIGH-DOSE CHEMOTHERAPY: No other medical and/or psychosocial problems which in the
opinion of the primary physician or principal investigator would place the patient at
unacceptable risk from this regimen

- HIGH-DOSE CHEMOTHERAPY: Greater than 2-week period of recovery from prior modality
used to control primary or recurrent site

Exclusion

- Histologically confirmed bone marrow metastases within 30 days prior to transplant;
prior bone marrow metastases with clearing of bone marrow (< 5% contamination as
measured by bilateral bone marrow biopsies) at the time for evaluation for this
protocol is acceptable

- Karnofsky performance status < 60% or Lansky performance status < 50% for patients
younger than 16 years old

- Females of reproductive age who are not using adequate birth control measures or who
are pregnant

- HIV disease

- Patients with prior treatment with myeloablative therapy are excluded