Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor
RATIONALE: Giving high-dose chemotherapy before an autologous stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.
PURPOSE: This clinical trial is studying how well giving busulfan, melphalan, and topotecan hydrochloride together with a stem cell transplant works in treating patients with newly diagnosed or relapsed solid tumor.
Adult Central Nervous System Germ Cell Tumor
Childhood Central Nervous System Germ Cell Tumor
Childhood Soft Tissue 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 Ovarian Germ Cell Tumor
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Unspecified Adult Solid Tumor, Protocol Specific
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
Procedure: autologous hematopoietic stem cell transplantation
Other: pharmacological study
Procedure: autologous bone marrow transplantation
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of High-Dose Chemotherapy With Busulfan, Melphalan, and Topotecan Followed by Autologous Hematopoietic Stem Cell Transplant in Advanced Stage and Recurrent Tumors|
- Treatment feasibility in terms of investigational agent-related adverse events of a novel treatment combination followed by peripheral blood stem cell rescue [ Time Frame: Day 100 post stem cell rescue ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: 1 year post stem cell rescue ] [ Designated as safety issue: No ]
- Disease-free survival [ Time Frame: 1 year post stem cell rescue ] [ Designated as safety issue: No ]
- Incidence of myeloid and platelet engraftment [ Time Frame: Day 100 post stem cell rescue ] [ Designated as safety issue: No ]
- Pharmacokinetics and pharmacodynamics of topotecan hydrochloride and busulfan [ Time Frame: Baseline through day 4 of investigational agent treatment ] [ Designated as safety issue: No ]
|Study Start Date:||December 2006|
|Estimated Primary Completion Date:||April 2019 (Final data collection date for primary outcome measure)|
Experimental: Arm I
See Detailed Description
Other Names:Drug: melphalan
Other Names:Drug: topotecan hydrochloride
Other Names:Other: laboratory biomarker analysis
Correlative studiesBiological: filgrastim
Given IV or subcutaneously
Other Names:Procedure: autologous hematopoietic stem cell transplantation
Undergo transplantationOther: pharmacological study
Other Name: pharmacological studiesProcedure: autologous bone marrow transplantation
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00638898
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|Principal Investigator:||Anna Pawlowska, MD||City of Hope Medical Center|