SarcomaPhase 2NCT00245011
Samarium Sm 153 and Stem Cell Transplant Followed By Radiation Therapy Patients With Osteosarcoma
A Phase 2 study testing filgrastim, ifosfamide and peripheral blood stem cell transplantation in people with Sarcoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to tumor cells and not harm normal cells. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and samarium Sm 153 lexidronam pentasodium. Read more about this study
- Who is it for?
- Ages 13 to 50 years
- Conditions the study is for
- Sarcoma
- What is being tested?
- filgrastim, ifosfamide and peripheral blood stem cell transplantation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2004to Mar 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 13 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of osteosarcoma
- High-risk disease, meeting 1 of the following criteria:
- Recurrent disease
- Refractory to conventional therapy
- Newly diagnosed metastatic disease with ≥ 4 pulmonary nodules or multiple bone lesions
- Unresectable primary tumor
Show all 15Show fewer
- Prior intralesional resection allowed
- Measurable disease by technetium Tc 99m diphosphonate bone scan
- Refractory to all standard therapies or highly unlikely to respond to conventional treatment
- Performance status Karnofsky 60-100%
- Life expectancy more than 8 weeks
- Absolute neutrophil count > 500/mm^3
- Platelet count > 50,000/mm^3
- Creatinine clearance > 70 mL/min OR * Radioisotope glomerular filtration rate normal
- Recovered from prior chemotherapy
Who cannot join
- Pregnant or nursing
- Positive pregnancy test for females of childbearing potential
- Fertile patients do not agree to use effective contraception
- Prior radiotherapy to the site of currently active disease
- Concurrent enrollment on protocol JHOC-J0094 allowed
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
About this study
Official title: High Dose Samarium-153 With Peripheral Blood Stem Cell Support in High Risk Osteogenic Sarcoma
RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to tumor cells and not harm normal cells. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and samarium Sm 153 lexidronam pentasodium. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving samarium Sm 153 lexidronam pentasodium together with a peripheral stem cell transplant and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving samarium Sm 153 lexidronam pentasodium together with autologous stem cell transplant and radiation therapy works in treating patients with recurrent or refractory, metastatic, or unresectable osteosarcoma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the clinical response in patients with recurrent or refractory, metastatic, or unresectable osteosarcoma treated with high-dose samarium Sm 153 lexidronam pentasodium (^153Sm-EDTMP) and autologous peripheral blood stem cell transplantation followed by external-beam radiotherapy.
- Correlate the amount of radiation delivered to a tumor with low-dose ^153Sm-EDTMP with that of high-dose ^153Sm-EDTMP in patients treated with this regimen.
Secondary
- Determine the overall and progression-free survival of patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine the long-term effects of this regimen in these patients.
- Determine the predictive value of fludeoxyglucose F 18 positron emission tomography (FDG-PET), diffusion-weighted MRI, and magnetic resonance spectroscopy for evaluation of treatment response in patients treated with this regimen.
OUTLINE: Patients are stratified according to resectability of the primary tumor (recurrent, refractory, or very high-risk disease vs unresectable primary tumor).
- Mobilization and collection of autologous peripheral blood stem cells (PBSCs)* : Patients receive ifosfamide IV daily for 5 days followed by filgrastim (G-CSF) subcutaneously daily. Patients then undergo leukapheresis for collection of autologous PBSCs until ≥ 2 x 10^6 CD34 (cluster of differentiation 34)-positive cells/kg are collected.
NOTE: *Patients who have undergone PBSC collection before study entry proceed to high-dose samarium Sm 153 lexidronam pentasodium (153Sm-EDTMP) infusion without mobilization and collection of autologous PBSCs.
- 153Sm-EDTMP infusion: Patients receive a trace dose of ^153Sm-EDTMP** IV over 1-2 minutes and undergo bone scan 4, 24, and 48-72 hours later. Six weeks later, patients receive high-dose ^153Sm-EDTMP IV over 1-2 minutes and undergo repeat bone scans 4, 24, and 48-72 hours later.
NOTE: **Patients may receive the trace dose on protocol JHOC (Johns Hopkins Oncology Center)-J0094.
- Autologous peripheral blood stem cell transplantation (PBSCT): Between 12-14 days after administration of high-dose ^153Sm-EDTMP, patients undergo autologous PBSCT. Beginning 2 days later, patients receive G-CSF IV daily.
- External-beam radiotherapy: Patients then undergo external-beam radiotherapy to the sites of bulky disease.
- Surgery: Some patients may also undergo surgical resection of residual disease. After completion of study treatment, patients are followed periodically for up to 3 years.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
- Conditions
- Sarcoma
- Being tested
- filgrastim, ifosfamide, peripheral blood stem cell transplantation, Sm-EDTMP (low dose), sm-EDTMP (higher dose)
- Keywords
- recurrent osteosarcoma, metastatic osteosarcoma, localized osteosarcoma
- Medical subject headings
- Sarcoma, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
Also called Neupogen
Filgrastim will be administered post post chemotherapy until target WBC (white blood cell) count is achieved.
ifosfamideDrug
Also called Ifex
Ifosfamide administered IV.
peripheral blood stem cell transplantationProcedure or surgery
Peripheral blood stem cell transplantation is done 14 days after 2nd dose of Samarium is delivered
Sm-EDTMP (low dose)Radiation
Sm-EDTMP (low dose) administered after autologous stem cell collection
sm-EDTMP (higher dose)Radiation
Upon blood cell count recovery from Sm-EDTMP (low dose), Sm-EDTMP (higher dose) is administered followed in 14 days by peripheral blood stem cell transplantation.
| Study group | Role | What they receive |
|---|---|---|
| Samarium-153 | Experimental | Cytoxan+Ifosfamide, Filgrastim pre samarium.'Sm-EDTMP (low dose). once counts recover, Sm-EDTMP (high dose) given. Peripheral blood stem cell transplantation is done 14 days later. Receives: Biological: filgrastim; Drug: ifosfamide; Procedure: peripheral blood stem cell transplantation; Radiation: Sm-EDTMP (low dose); Radiation: sm-EDTMP (higher dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response
WHO (World Health Organization) tumor measurement criteria used to determine response.
Measured: 1 week after study treatment
Secondary outcomes (5)
Predictive Value of Imaging Studies
Measured: At Time of Tumor Resection
Overall and Progression-free Survival After Study Treatment
Measured: up to 4 years
Toxicity at End of Study Treatment
Measured: Continual and at End of Study
Long Term Side Effects of Infusional Samarium-153 After Study Treatment
Measured: Continual
Correlative Dose of Radiation by Low Dose and High Dose Samarium-153
Measured: completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2005 (estimated)
- Study startOct 2004
- Primary completionOct 2008
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for SarcomaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- David M. Loeb, MD, PhD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00245011
- Sponsor's protocol ID
- J0347
- Other IDs
- JHOC-J0347, 03-09-08-02, CDR0000447134
- Status last verified
- Mar 2020
- First submitted
- 25 Oct 2005
- Last updated
- 10 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Senthamizhchelvan S, Hobbs RF, Song H, Frey EC, Zhang Z, Armour E, Wahl RL, Loeb DM, Sgouros G. Tumor dosimetry and response for 153Sm-ethylenediamine tetramethylene phosphonic acid therapy of high-risk osteosarcoma. J Nucl Med. 2012 Feb;53(2):215-24. doi: 10.2967/jnumed.111.096677. Epub 2012 Jan 17.
PubMed 22251554Loeb DM, Hobbs RF, Okoli A, Chen AR, Cho S, Srinivasan S, Sgouros G, Shokek O, Wharam MD Jr, Scott T, Schwartz CL. Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma. Cancer. 2010 Dec 1;116(23):5470-8. doi: 10.1002/cncr.25518. Epub 2010 Aug 16.
PubMed 20715156Loeb DM, Garrett-Mayer E, Hobbs RF, Prideaux AR, Sgouros G, Shokek O, Wharam MD Jr, Scott T, Schwartz CL. Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer. 2009 Jun 1;115(11):2514-22. doi: 10.1002/cncr.24286.
PubMed 19338063
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Dose Samarium-153 With Peripheral Blood Stem Cell Support in High Risk Osteogenic Sarcoma
- ClinicalTrials.gov ID
- NCT00245011
- Acronym / sponsor ID
- J0347
- Conditions
- Sarcoma
- Keywords
- recurrent osteosarcoma, metastatic osteosarcoma, localized osteosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2004
- Primary completion
- Oct 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 27 Oct 2005 (estimated)
- Results
- Posted 1 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Radioactive drugs, such as samarium Sm 153 lexidronam pentasodium, may carry radiation directly to tumor cells and not harm normal cells. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and samarium Sm 153 lexidronam pentasodium. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving samarium Sm 153 lexidronam pentasodium together with a peripheral stem cell transplant and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving samarium Sm 153 lexidronam pentasodium together with autologous stem cell transplant and radiation therapy works in treating patients with recurrent or refractory, metastatic, or unresectable osteosarcoma.
Detailed description
OBJECTIVES:
Primary
- Determine the clinical response in patients with recurrent or refractory, metastatic, or unresectable osteosarcoma treated with high-dose samarium Sm 153 lexidronam pentasodium (^153Sm-EDTMP) and autologous peripheral blood stem cell transplantation followed by external-beam radiotherapy.
- Correlate the amount of radiation delivered to a tumor with low-dose ^153Sm-EDTMP with that of high-dose ^153Sm-EDTMP in patients treated with this regimen.
Secondary
- Determine the overall and progression-free survival of patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine the long-term effects of this regimen in these patients.
- Determine the predictive value of fludeoxyglucose F 18 positron emission tomography (FDG-PET), diffusion-weighted MRI, and magnetic resonance spectroscopy for evaluation of treatment response in patients treated with this regimen.
OUTLINE: Patients are stratified according to resectability of the primary tumor (recurrent, refractory, or very high-risk disease vs unresectable primary tumor).
- Mobilization and collection of autologous peripheral blood stem cells (PBSCs)* : Patients receive ifosfamide IV daily for 5 days followed by filgrastim (G-CSF) subcutaneously daily. Patients then undergo leukapheresis for collection of autologous PBSCs until ≥ 2 x 10^6 CD34 (cluster of differentiation 34)-positive cells/kg are collected.
NOTE: *Patients who have undergone PBSC collection before study entry proceed to high-dose samarium Sm 153 lexidronam pentasodium (153Sm-EDTMP) infusion without mobilization and collection of autologous PBSCs.
- 153Sm-EDTMP infusion: Patients receive a trace dose of ^153Sm-EDTMP** IV over 1-2 minutes and undergo bone scan 4, 24, and 48-72 hours later. Six weeks later, patients receive high-dose ^153Sm-EDTMP IV over 1-2 minutes and undergo repeat bone scans 4, 24, and 48-72 hours later.
NOTE: **Patients may receive the trace dose on protocol JHOC (Johns Hopkins Oncology Center)-J0094.
- Autologous peripheral blood stem cell transplantation (PBSCT): Between 12-14 days after administration of high-dose ^153Sm-EDTMP, patients undergo autologous PBSCT. Beginning 2 days later, patients receive G-CSF IV daily.
- External-beam radiotherapy: Patients then undergo external-beam radiotherapy to the sites of bulky disease.
- Surgery: Some patients may also undergo surgical resection of residual disease. After completion of study treatment, patients are followed periodically for up to 3 years.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Samarium-153 | Experimental | Biological: filgrastim, Drug: ifosfamide, Procedure: peripheral blood stem cell transplantation, Radiation: Sm-EDTMP (low dose), Radiation: sm-EDTMP (higher dose)Cytoxan+Ifosfamide, Filgrastim pre samarium.'Sm-EDTMP (low dose). once counts recover, Sm-EDTMP (high dose) given. Peripheral blood stem cell transplantation is done 14 days later. |
Who may qualify
- Ages
- 13 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- Diagnosis of osteosarcoma
- Measurable disease by technetium Tc 99m diphosphonate bone scan
- Refractory to all standard therapies or highly unlikely to respond to conventional treatment
- Performance status Karnofsky 60-100%
- Life expectancy more than 8 weeks
Key exclusion criteria (5 listed)
- Pregnant or nursing
- Positive pregnancy test for females of childbearing potential
- Fertile patients do not agree to use effective contraception
- Prior radiotherapy to the site of currently active disease
- Concurrent enrollment on protocol JHOC-J0094 allowed
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 |
|---|---|---|
| filgrastimAlso: NeupogenFilgrastim will be administered post post chemotherapy until target WBC (white blood cell) count is achieved. | Biological | Samarium-153 |
| ifosfamideAlso: IfexIfosfamide administered IV. | Drug | Samarium-153 |
| peripheral blood stem cell transplantationPeripheral blood stem cell transplantation is done 14 days after 2nd dose of Samarium is delivered | Procedure or surgery | Samarium-153 |
| Sm-EDTMP (low dose)Sm-EDTMP (low dose) administered after autologous stem cell collection | Radiation | Samarium-153 |
| sm-EDTMP (higher dose)Upon blood cell count recovery from Sm-EDTMP (low dose), Sm-EDTMP (higher dose) is administered followed in 14 days by peripheral blood stem cell transplantation. | Radiation | Samarium-153 |
Primary outcome
Tumor Response
Time frame: 1 week after study treatment
WHO (World Health Organization) tumor measurement criteria used to determine response.
5 secondary outcomes
Predictive Value of Imaging Studies
Time frame: At Time of Tumor Resection
Overall and Progression-free Survival After Study Treatment
Time frame: up to 4 years
Toxicity at End of Study Treatment
Time frame: Continual and at End of Study
Long Term Side Effects of Infusional Samarium-153 After Study Treatment
Time frame: Continual
Correlative Dose of Radiation by Low Dose and High Dose Samarium-153
Time frame: completion of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22251554Senthamizhchelvan S, Hobbs RF, Song H, Frey EC, Zhang Z, Armour E, Wahl RL, Loeb DM, Sgouros G. Tumor dosimetry and response for 153Sm-ethylenediamine tetramethylene phosphonic acid therapy of high-risk osteosarcoma. J Nucl Med. 2012 Feb;53(2):215-24. doi: 10.2967/jnumed.111.096677. Epub 2012 Jan 17.
- Results publication: PubMed 20715156Loeb DM, Hobbs RF, Okoli A, Chen AR, Cho S, Srinivasan S, Sgouros G, Shokek O, Wharam MD Jr, Scott T, Schwartz CL. Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma. Cancer. 2010 Dec 1;116(23):5470-8. doi: 10.1002/cncr.25518. Epub 2010 Aug 16.
- Results publication: PubMed 19338063Loeb DM, Garrett-Mayer E, Hobbs RF, Prideaux AR, Sgouros G, Shokek O, Wharam MD Jr, Scott T, Schwartz CL. Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma. Cancer. 2009 Jun 1;115(11):2514-22. doi: 10.1002/cncr.24286.
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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.
David M. Loeb, MD, PhD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing filgrastim, ifosfamide and peripheral blood stem cell transplantation in people with Sarcoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 15 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 10 Mar 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tumor Response (time frame: 1 week after study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00245011, which also lists 3 linked publications.
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 10 Mar 2020.