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

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ClinicalTrials.gov Identifier: NCT00638898
Recruitment Status : Active, not recruiting
First Posted : March 19, 2008
Last Update Posted : February 17, 2021
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE March 18, 2008
First Posted Date  ICMJE March 19, 2008
Last Update Posted Date February 17, 2021
Actual Study Start Date  ICMJE February 26, 2007
Estimated Primary Completion Date December 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 13, 2010)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2008)
Treatment feasibility in terms of investigational agent-related adverse events of a novel treatment combination followed by peripheral blood stem cell rescue
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2010)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2008)
  • Overall survival
  • Disease-free survival
  • Incidence of myeloid and platelet engraftment
  • Pharmacokinetics and pharmacodynamics of topotecan hydrochloride and busulfan
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor
Official Title  ICMJE Pilot Study of High-Dose Chemotherapy With Busulfan, Melphalan, and Topotecan Followed by Autologous Hematopoietic Stem Cell Transplant in Advanced Stage and Recurrent Tumors
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Arm I
See Detailed Description
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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 11, 2010)
25
Original Enrollment  ICMJE
 (submitted: March 18, 2008)
20
Estimated Study Completion Date  ICMJE December 30, 2021
Estimated Primary Completion Date December 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 40 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00638898
Other Study ID Numbers  ICMJE 03112
NCI-2009-01600 ( Registry Identifier: CDR0000589296 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anna Pawlowska, MD City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP