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Pilot Study of High-Dose Chemotherapy With Busulfan, Melphalan, and Topotecan Followed by Autologous Hematopoietic Stem Cell Transplant in Advanced Stage and Recurrent Tumors


N/A
6 Months
40 Years
Open (Enrolling)
Both
Solid Tumor, Adult Central Nervous System Germ Cell Tumor, Adult Rhabdomyosarcoma, Childhood Central Nervous System Germ Cell Tumor, Childhood Soft Tissue Sarcoma, Ewing Sarcoma, Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Ovarian Mixed Germ Cell Tumor, Previously Untreated Childhood Rhabdomyosarcoma, Recurrent Adult Brain Tumor, Recurrent Adult Soft Tissue Sarcoma, Recurrent Childhood Brain Stem Glioma, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Malignant Germ Cell Tumor, Recurrent Childhood Medulloblastoma, Recurrent Childhood Pineoblastoma, Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor, Recurrent Childhood Visual Pathway and Hypothalamic Glioma, Recurrent Childhood Visual Pathway Glioma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Extragonadal Germ Cell Tumor, Recurrent Extragonadal Non-seminomatous Germ Cell Tumor, Recurrent Malignant Testicular Germ Cell Tumor, Recurrent Neuroblastoma, Recurrent Ovarian Germ Cell Tumor, Recurrent Wilms Tumor and Other Childhood Kidney Tumors, Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

Pilot Study of High-Dose Chemotherapy With Busulfan, Melphalan, and Topotecan Followed by Autologous Hematopoietic Stem Cell Transplant in Advanced Stage and Recurrent Tumors


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 Criteria


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment feasibility in terms of investigational agent-related adverse events of a novel treatment combination followed by peripheral blood stem cell rescue

Outcome Time Frame:

Day 100 post stem cell rescue

Safety Issue:

Yes

Principal Investigator

Anna Pawlowska, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Institutional Review Board

Study ID:

03112

NCT ID:

NCT00638898

Start Date:

December 2006

Completion Date:

Related Keywords:

  • Solid Tumor
  • Adult Central Nervous System Germ Cell Tumor
  • Adult Rhabdomyosarcoma
  • Childhood Central Nervous System Germ Cell Tumor
  • Childhood Soft Tissue Sarcoma
  • Ewing Sarcoma
  • Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Ovarian Mixed Germ Cell Tumor
  • Previously Untreated Childhood Rhabdomyosarcoma
  • Recurrent Adult Brain Tumor
  • Recurrent Adult Soft Tissue Sarcoma
  • Recurrent Childhood Brain Stem Glioma
  • Recurrent Childhood Cerebellar Astrocytoma
  • Recurrent Childhood Cerebral Astrocytoma
  • Recurrent Childhood Ependymoma
  • Recurrent Childhood Malignant Germ Cell Tumor
  • Recurrent Childhood Medulloblastoma
  • Recurrent Childhood Pineoblastoma
  • Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
  • Recurrent Childhood Visual Pathway and Hypothalamic Glioma
  • Recurrent Childhood Visual Pathway Glioma
  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Recurrent Extragonadal Germ Cell Tumor
  • Recurrent Extragonadal Non-seminomatous Germ Cell Tumor
  • Recurrent Malignant Testicular Germ Cell Tumor
  • Recurrent Neuroblastoma
  • Recurrent Ovarian Germ Cell Tumor
  • Recurrent Wilms Tumor and Other Childhood Kidney Tumors
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Astrocytoma
  • Brain Neoplasms
  • Ependymoma
  • Glioma
  • Kidney Neoplasms
  • Medulloblastoma
  • Wilms Tumor
  • Neuroblastoma
  • Rhabdomyosarcoma
  • Testicular Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Pinealoma
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Rhabdomyosarcoma, Embryonal
  • Sarcoma
  • Germinoma
  • Ovarian Neoplasms
  • Optic Nerve Glioma
  • Neoplasms
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral

Name

Location

City of HopeDuarte, California  91010