This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00638898
First received: March 18, 2008
Last updated: May 4, 2017
Last verified: May 2017
  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 hydrochloride together with a stem cell transplant works in treating patients with newly diagnosed or relapsed solid tumor.


Condition Intervention
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 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

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 [ Time Frame: Day 100 post stem cell rescue ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 1 year post stem cell rescue ]
  • Disease-free survival [ Time Frame: 1 year post stem cell rescue ]
  • Incidence of myeloid and platelet engraftment [ Time Frame: Day 100 post stem cell rescue ]
  • Pharmacokinetics and pharmacodynamics of topotecan hydrochloride and busulfan [ Time Frame: Baseline through day 4 of investigational agent treatment ]

Estimated Enrollment: 25
Actual Study Start Date: December 11, 2006
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
See Detailed Description
Drug: busulfan
Given IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Myelosan
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
  • Melfalan
Drug: topotecan hydrochloride
Given IV
Other Names:
  • hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • TOPO
Other: laboratory biomarker analysis
Correlative studies
Biological: filgrastim
Given IV or subcutaneously
Other Names:
  • G-CSF
  • granulocyte colony-stimulating factor
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
Procedure: autologous hematopoietic stem cell transplantation
Undergo transplantation
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Procedure: autologous bone marrow transplantation
Undergo transplantation
Other Names:
  • ABMT
  • bone marrow transplantation, autologous
  • transplantation, autologous bone marrow

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.

  Eligibility

Ages Eligible for Study:   6 Months to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Anna Pawlowska, MD City of Hope Medical Center
  More Information

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00638898     History of Changes
Other Study ID Numbers: 03112
NCI-2009-01600 ( Registry Identifier: CDR0000589296 )
Study First Received: March 18, 2008
Last Updated: May 4, 2017

Additional relevant MeSH terms:
Sarcoma, Ewing
Neoplasms
Sarcoma
Glioma
Neuroblastoma
Neoplasms, Germ Cell and Embryonal
Astrocytoma
Rhabdomyosarcoma
Ependymoma
Germinoma
Ovarian Neoplasms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Medulloblastoma
Testicular Neoplasms
Wilms Tumor
Rhabdomyosarcoma, Embryonal
Neuroectodermal Tumors, Primitive, Peripheral
Kidney Neoplasms
Optic Nerve Glioma
Pinealoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Osteosarcoma
Neoplasms, Bone Tissue

ClinicalTrials.gov processed this record on August 22, 2017