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

NCT00638898 | Completed Phase 1 DMC

• 2 other identifiers: 03112NCI-2009-01600
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall survival

  1 year post stem cell rescue

• Disease-free survival

  1 year post stem cell rescue

• 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

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description

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

Interventions

busulfan DRUG

Given IV

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon, Myelosan

Arm I

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin, Melfalan

Arm I

topotecan hydrochloride DRUG

Given IV

Also known as: hycamptamine, Hycamtin, SKF S-104864-A, TOPO

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

filgrastim BIOLOGICAL

Given IV or subcutaneously

Also known as: G-CSF, granulocyte colony-stimulating factor, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

Arm I

autologous hematopoietic stem cell transplantation PROCEDURE

Undergo transplantation

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

autologous bone marrow transplantation PROCEDURE

Undergo transplantation

Also known as: ABMT, bone marrow transplantation, autologous, transplantation, autologous bone marrow

Arm I

Eligibility Criteria

• Age: 6 Months - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Rhabdomyosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive, Peripheral; Brain Neoplasms; Sarcoma; Astrocytoma; Familial ependymoma; Medulloblastoma; Optic Nerve Glioma; Testicular Neoplasms; Neuroblastoma; Wilms Tumor

Interventions

Busulfan; Melphalan; Topotecan; trioctyl phosphine oxide; Filgrastim; Granulocyte Colony-Stimulating Factor; Bone Marrow Transplantation; Transplantation

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Camptothecin; Alkaloids; Heterocyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Anna Pawlowska, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2008
• First Posted: March 19, 2008
• Study Start: February 26, 2007
• Primary Completion: January 19, 2013
• Study Completion: December 10, 2024
• Last Updated: March 20, 2025

Record last verified: 2025-03

Locations

US (1)