Solid TumorPhase 1NCT00638898
Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor
A Phase 1 study testing busulfan, melphalan and topotecan hydrochloride in people with Solid Tumor and Adult Central Nervous System Germ Cell Tumor, run by City of Hope Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 6 months to 40 years
- Conditions the study is for
- Solid Tumor, Adult Central Nervous System Germ Cell Tumor, Adult Rhabdomyosarcoma
- What is being tested?
- busulfan, melphalan and topotecan hydrochloride
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Feb 2007to 10 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
OBJECTIVES:
- 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.
- 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
- Being tested
- busulfan, melphalan, topotecan hydrochloride, laboratory biomarker analysis, filgrastim
- Medical subject headings
- Rhabdomyosarcoma, Sarcoma, Ewing, Neuroectodermal Tumors, Primitive, Peripheral, Brain Neoplasms, Sarcoma, Astrocytoma, Familial ependymoma, Medulloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
busulfanDrug
Also called BSF, BU, Misulfan, Mitosan
Given IV
melphalanDrug
Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard
Given IV
topotecan hydrochlorideDrug
Also called hycamptamine, Hycamtin, SKF S-104864-A, TOPO
Given IV
laboratory biomarker analysisOther
Correlative studies
filgrastimBiological
Also called G-CSF, granulocyte colony-stimulating factor, Neupogen, r-metHuG-CSF
Given IV or subcutaneously
autologous hematopoietic stem cell transplantationProcedure or surgery
Undergo transplantation
Also called pharmacological studies
Correlative studies
autologous bone marrow transplantationProcedure or surgery
Also called ABMT, bone marrow transplantation, autologous, transplantation, autologous bone marrow
Undergo transplantation
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | See Detailed Description Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment feasibility in terms of investigational agent-related adverse events of a novel treatment combination followed by peripheral blood stem cell rescue
Measured: Day 100 post stem cell rescue
Secondary outcomes (4)
Overall survival
Measured: 1 year post stem cell rescue
Disease-free survival
Measured: 1 year post stem cell rescue
Incidence of myeloid and platelet engraftment
Measured: Day 100 post stem cell rescue
Pharmacokinetics and pharmacodynamics of topotecan hydrochloride and busulfan
Measured: Baseline through day 4 of investigational agent treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2008 (estimated)
- Study start26 Feb 2007
- Primary completion19 Jan 2013
- Study completion10 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anna Pawlowska, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00638898
- Sponsor's protocol ID
- 03112
- Other IDs
- NCI-2009-01600
- Status last verified
- Mar 2025
- First submitted
- 18 Mar 2008
- Last updated
- 20 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00638898
- Acronym / sponsor ID
- 03112
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Study start
- 26 Feb 2007 (actual)
- Primary completion
- 19 Jan 2013 (actual)
- Study completion
- 10 Dec 2024 (actual)
- First posted
- 19 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | 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 transplantationSee Detailed Description |
Who may qualify
- Ages
- 6 months to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| busulfanAlso: BSF, BU, Misulfan, MitosanGiven IV | Drug | Arm I |
| melphalanAlso: Alkeran, CB-3025, L-PAM, L-phenylalanine mustardGiven IV | Drug | Arm I |
| topotecan hydrochlorideAlso: hycamptamine, Hycamtin, SKF S-104864-A, TOPOGiven IV | Drug | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
| filgrastimAlso: G-CSF, granulocyte colony-stimulating factor, Neupogen, r-metHuG-CSFGiven IV or subcutaneously | Biological | Arm I |
| autologous hematopoietic stem cell transplantationUndergo transplantation | Procedure or surgery | Arm I |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I |
| autologous bone marrow transplantationAlso: ABMT, bone marrow transplantation, autologous, transplantation, autologous bone marrowUndergo transplantation | Procedure or surgery | Arm I |
Primary outcome
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
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
Related trials for Solid Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anna Pawlowska, MD principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing busulfan, melphalan and topotecan hydrochloride in people with Solid Tumor and Adult Central Nervous System Germ Cell Tumor, run by City of Hope Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025.