Busulfan, Melphalan, Topotecan, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor - Full Text View

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00638898

Purpose

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 together with a stem cell transplant works in treating patients with newly diagnosed or relapsed solid tumor.

Condition	Intervention
Brain and Central Nervous System Tumors Childhood Germ Cell Tumor Extragonadal Germ Cell Tumor Kidney Cancer Neuroblastoma Ovarian Cancer Sarcoma Testicular Germ Cell Tumor Unspecified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific	Drug: busulfan Drug: filgrastim Drug: melphalan Drug: topotecan hydrochloride Procedure: autologous bone marrow transplantation Procedure: autologous hematopoietic stem cell transplantation Procedure: pharmacological study

MedlinePlus related topics: Bone Marrow Transplantation Cancer Kidney Cancer Neuroblastoma Ovarian Cancer Soft Tissue Sarcoma

Drug Information available for: Filgrastim Melphalan Topotecan hydrochloride Topotecan Melphalan hydrochloride Sarcolysin Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Treatment feasibility in terms of investigational agent-related adverse events of a novel treatment combination followed by peripheral blood stem cell rescue [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: Yes ]
Disease-free survival [ Designated as safety issue: Yes ]
Incidence of myeloid and platelet engraftment [ Designated as safety issue: No ]
Pharmacokinetics and pharmacodynamics of topotecan hydrochloride and busulfan [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	December 2006
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To assess the feasibility of a novel combination conditioning therapy comprising high-dose busulfan, melphalan, and topotecan hydrochloride followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with newly diagnosed, relapsed, refractory and/or poor risk pediatric solid tumors.
To determine myeloid and platelet engraftment, overall survival and disease-free survival in these patients and in patients who have solid tumors with poor risk factors at the time of diagnosis.
To determine the pharmacokinetics of topotecan hydrochloride.

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.

Patients undergo blood sample collection periodically for pharmacological and pharmacodynamic studies.

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

Eligibility

Ages Eligible for Study:	up to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of 1 of the following:
- Relapsed disease, including any of the following:
  - Neuroblastoma*
  - Rhabdomyosarcoma
  - Ewing Sarcoma
  - PNET
  - Brain tumors*
  - Soft tissue sarcoma
  - Wilms tumor
  - Germ cell tumors
  - Other solid tumors that achieve at least a partial response (PR) to chemotherapy, surgery, or radiotherapy (not including lung fields)
- Newly diagnosed, poor-risk pediatric solid tumors, including any of the following:
  - Metastatic Ewing sarcoma
  - Metastatic PNET
  - Rhabdomyosarcoma
  - Soft tissue sarcoma
  - Ectomesenchymoma
  - Other solid tumors, meeting the following criteria:
    - Very high risk for relapse
    - Achieved at least a PR to chemotherapy, surgery, or radiotherapy (not including lung fields) NOTE: *Histologically confirmed diagnosis of brain stem tumors is not required; demonstrations of marrow metastases with elevated urinary catecholamines is adequate for diagnosis in patients with neuroblastoma.
Must be in complete response (CR) or partial response (PR) at the primary site
No histologically confirmed bone marrow metastases within 30 days prior to transplantation
- Prior bone marrow metastasis with clearing of bone marrow (< 5% contamination as measured by bilateral bone marrow biopsies) at the time of evaluation for this protocol is acceptable

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 60-100% OR Lansky PS 50-100% (patients < 16 years of age)
Absolute granulocyte count > 750/μL
Platelet count > 50,000/μL
Bilirubin < 2 g/dL
SGOT and SGPT < 5 times upper limit of normal
Creatinine clearance by 12- or 24-hour urine collection or glomerular filtration rate > 60 mL/min
Not pregnant
Fertile patients must use effective contraception
Ejection fraction > 55% by ECHO or MUGA scan
FEV_1 > 2 liters room air (adults)
DLCO > 50% predicted
No HIV disease
No contraindications to the stem cell collection by apheresis or by bone marrow harvesting
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

PRIOR CONCURRENT THERAPY:

Recovered for more than 2 weeks from prior therapy to control disease at primary or recurrent site
No prior myeloablative therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638898

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Ellen Bolotin, MD

Beckman Research Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000589296, CHNMC-03112
Study First Received:	March 18, 2008
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00638898
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent neuroblastoma
adult rhabdomyosarcoma
previously untreated childhood rhabdomyosarcoma
recurrent adult brain tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
Ewing sarcoma
recurrent adult soft tissue sarcoma
adult central nervous system germ cell tumor
ovarian mixed germ cell tumor
recurrent childhood malignant germ cell tumor
recurrent extragonadal germ cell tumor
recurrent extragonadal non-seminomatous germ cell tumor
recurrent malignant testicular germ cell tumor
recurrent ovarian germ cell tumor
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor

childhood soft tissue sarcoma
unspecified adult solid tumor, protocol specific
unspecified childhood solid tumor, protocol specific
recurrent Wilms tumor and other childhood kidney tumors
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood brain stem glioma
recurrent childhood ependymoma
recurrent childhood medulloblastoma
recurrent childhood pineoblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood visual pathway glioma
childhood central nervous system germ cell tumor
adult central nervous system germ cell tumor

Study placed in the following topic categories:

Neuroectodermal Tumors, Primitive
Malignant mesenchymal tumor
Urogenital Neoplasms
Nonseminomatous germ cell tumor
Central Nervous System Neoplasms
Urologic Neoplasms
Neoplasms, Connective and Soft Tissue
Ewing's sarcoma
Neuroepithelioma
Glioma
Kidney Diseases
Nervous System Neoplasms
Rhabdomyosarcoma
Endocrine Gland Neoplasms
Astrocytoma

Genital Neoplasms, Female
Endocrine System Diseases
Testicular Neoplasms
Renal cancer
Carcinoma
Brain Neoplasms
Neuroectodermal Tumors
Sarcoma
Testicular cancer
Topotecan
Neoplasms, Glandular and Epithelial
Melphalan
Gonadal Disorders
Ewing's family of tumors
Ovarian Diseases

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Nervous System Diseases
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Enzyme Inhibitors
Immunosuppressive Agents

Pharmacologic Actions
Adnexal Diseases
Neoplasms
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009