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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00638898
• Other study ID #: 03112
• Secondary ID: NCI-2009-01600
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 26, 2007
• Est. completion date: December 30, 2024

Study information

• Verified date: March 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: December 30, 2024
• Est. primary completion date: January 19, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Adult Central Nervous System Germ Cell Tumor
• Adult Rhabdomyosarcoma
• Astrocytoma
• Childhood Central Nervous System Germ Cell Tumor
• Childhood Soft Tissue Sarcoma
• Ependymoma
• Ewing Sarcoma
• Glioma
• Medulloblastoma
• Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Neuroblastoma
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Neuroectodermal Tumors, Primitive, Peripheral
• Ovarian Mixed Germ Cell Tumor
• Pinealoma
• Previously Untreated Childhood Rhabdomyosarcoma
• Recurrence
• 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
• Rhabdomyosarcoma
• Sarcoma
• Sarcoma, Ewing
• Solid Tumor
• Testicular Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific
• Unspecified Childhood Solid Tumor, Protocol Specific
• Wilms Tumor

Intervention

Drug:
• busulfan
Given IV
• melphalan
Given IV
• topotecan hydrochloride
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Biological:
• filgrastim
Given IV or subcutaneously

Procedure:
• autologous hematopoietic stem cell transplantation
Undergo transplantation

Other:
• pharmacological study
Correlative studies

Procedure:
• autologous bone marrow transplantation
Undergo transplantation

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
City of Hope Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival		1 year post stem cell rescue
Secondary	Disease-free survival		1 year post stem cell rescue
Secondary	Incidence of myeloid and platelet engraftment		Day 100 post stem cell rescue
Secondary	Pharmacokinetics and pharmacodynamics of topotecan hydrochloride and busulfan		Baseline through day 4 of investigational agent treatment