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

Phase 1

Completed

• Conditions: Childhood Soft Tissue Sarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Childhood Central Nervous System Germ Cell Tumor; Ewing Sarcoma; Ovarian Mixed Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Previously Untreated Childhood Rhabdomyosarcoma
• Interventions: Drug: busulfan; Drug: melphalan; Drug: topotecan hydrochloride; Other: laboratory biomarker analysis; Biological: filgrastim; Procedure: autologous hematopoietic stem cell transplantation; Other: pharmacological study; Procedure: autologous bone marrow transplantation

• Registration Number: NCT00638898
• Lead Sponsor: City of Hope Medical Center

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2007-02-26
• Study First Submitted: 2008-03-18
• Study First Submitted QC: 2008-03-18
• Study First Posted: 2008-03-19
• Primary Completion: 2013-01-19
• Study Completion: 2024-12-10
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-18
• Last Update Posted: 2025-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	topotecan hydrochloride	See Detailed Description
Arm I	busulfan	See Detailed Description
Arm I	filgrastim	See Detailed Description
Arm I	autologous bone marrow transplantation	See Detailed Description
Arm I	laboratory biomarker analysis	See Detailed Description
Arm I	autologous hematopoietic stem cell transplantation	See Detailed Description
Arm I	pharmacological study	See Detailed Description
Arm I	melphalan	See Detailed Description

Primary Outcome Measures

Name	Time	Method
Treatment feasibility in terms of investigational agent-related adverse events of a novel treatment combination followed by peripheral blood stem cell rescue	Day 100 post stem cell rescue

Secondary Outcome Measures

Name	Time	Method
Incidence of myeloid and platelet engraftment	Day 100 post stem cell rescue
Pharmacokinetics and pharmacodynamics of topotecan hydrochloride and busulfan	Baseline through day 4 of investigational agent treatment
Overall survival	1 year post stem cell rescue
Disease-free survival	1 year post stem cell rescue

Trial Locations

Locations (1)

City of Hope; 🇺🇸 Duarte, California, United States