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| ID | Type | Description | Link |
|---|---|---|---|
| JHOC-J0347 | Other Identifier | Johns Hopkins University Clinical Research Office (CRO) | |
| 03-09-08-02 | Other Identifier | JHM IRB | |
| CDR0000447134 | Registry Identifier | NCI PDQ |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients are stratified according to resectability of the primary tumor (recurrent, refractory, or very high-risk disease vs unresectable primary tumor).
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.
NOTE: **Patients may receive the trace dose on protocol JHOC (Johns Hopkins Oncology Center)-J0094.
PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| filgrastim | Biological | Filgrastim will be administered post post chemotherapy until target WBC (white blood cell) count is achieved. |
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| Measure | Description | Time Frame |
|---|---|---|
| Tumor Response | WHO (World Health Organization) tumor measurement criteria used to determine response. | 1 week after study treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Predictive Value of Imaging Studies | At Time of Tumor Resection | |
| Overall and Progression-free Survival After Study Treatment | up to 4 years | |
| Toxicity at End of Study Treatment |
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Inclusion
Diagnosis of osteosarcoma
High-risk disease, meeting 1 of the following criteria:
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
Exclusion
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| Name | Affiliation | Role |
|---|---|---|
| David M. Loeb, MD, PhD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21231-2410 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22251554 | Result | 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. | |
| 20715156 | Result |
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| ID | Title | Description |
|---|---|---|
| FG000 | Samarium-153/Stem Cell Transplant/Radiation | Samarium Sm153 Lexidronam Pentasodium (Samarium)/Stem Cell Transplant/Radiation arm: receive Ifosphamide IV in preparation for peripheral blood stem cell transplant followed by collection of stem cells. Samarium is administered after collection of peripheral blood stem cells (PBCT). Once counts recover, while receiving filgrastim daily, a second, higher dose of Samarium-153 is given, followed in 14 days by infusion of the stem cells. Filgrastim: administered daily until count recovery Ifosfamide: administered as part of Stem Cell transplant preparation. PBCT: Before administration of Samarium, collection of autologous hematopoietic stem cells Radiation: Radiation Dosimetry performed at 4, 24, 48, and 72 after each infusion of Sm-EDTMP. Samarium: First dose is administered after autologous stem cell collection. Second, higher dose, of SM-EDTMP administered after count recover. 14 days after administration of higher dose, patient undergoes autologous stem cell infusion. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| ifosfamide | Drug | Ifosfamide administered IV. |
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| peripheral blood stem cell transplantation | Procedure | Peripheral blood stem cell transplantation is done 14 days after 2nd dose of Samarium is delivered |
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| Sm-EDTMP (low dose) | Radiation | Sm-EDTMP (low dose) administered after autologous stem cell collection |
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| 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. |
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| Continual and at End of Study |
| Long Term Side Effects of Infusional Samarium-153 After Study Treatment | Continual |
| Correlative Dose of Radiation by Low Dose and High Dose Samarium-153 | completion of treatment |
| Loeb 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. |
| 19338063 | Result | Loeb 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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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Samarium-153/Stem Cell Transplant/Radiation | Samarium Sm153 Lexidronam Pentasodium/Stem Cell Transplant/Radiation arm will receive Ifosphamide IV in preparation for peripheral blood stem cell transplant followed by stem cell collection. Samarium Sm153 Lexidronam Pentasodium is administered after collection of peripheral blood stem cells. Once counts recover, while receiving filgrastim daily, a 2nd, higher dose of Samarium-153 is given, followed in 14 days by stem cell infusion. Filgrastim: Filgrastim will be administered every day til count recovery Ifosfamide: Ifosfamide will be administered as part of Stem Cell transplant prep. Peripheral blood stem cell transplantation: Before administration of Samarium, collection of autologous hematopoietic stem cells Radiation: Radiation Dosimetry performed at 4, 24, 48, and 72 after each infusion of Sm-EDTMP. Samarium Sm 153 lexidronam pentasodium: First dose of Sm-EDTMP administered after autologous stem cell collection. Second, higher dose, of SM-EDTMP administered 7 days later. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Tumor Response | WHO (World Health Organization) tumor measurement criteria used to determine response. | 11 subjects, heavily treated with chemotherapy with osteosarcoma metastatic to bone were enrolled; 10 evaluable for response. | Posted | Number | participants | 1 week after study treatment |
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| Secondary | Predictive Value of Imaging Studies | The PI has left the institution and the only access to the data is from publications. The access to this specific information/data cannot be confirmed and is not available to be reported. | Posted | At Time of Tumor Resection |
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| Secondary | Overall and Progression-free Survival After Study Treatment | Posted | Median | Full Range | days | up to 4 years |
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| Secondary | Toxicity at End of Study Treatment | Posted | Count of Participants | Participants | Continual and at End of Study |
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| Secondary | Long Term Side Effects of Infusional Samarium-153 After Study Treatment | The PI has left the institution and the only access to the data is from publications. The access to this specific information/data cannot be confirmed and is not available to be reported | Posted | Continual |
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| Secondary | Correlative Dose of Radiation by Low Dose and High Dose Samarium-153 | The PI has left the institution and the only access to the data is from publications. The access to this specific information/data cannot be confirmed and is not available to be reported | Posted | completion of treatment |
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6 weeks; the dose limiting toxicity was defined to be recovery of blood counts by 6 weeks post treatment with SmEDTMP (higher dose). Subjects continued to be monitored until count recovery and indefinitely for survival.
The PI has left the institution and the only access to the data is from publications. The access to all-cause mortality data cannot be confirmed and is not available to be reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Samarium-153 | 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. filgrastim: Filgrastim will be administered post post chemotherapy until target WBC count is achieved. ifosfamide: Ifosfamide administered IV. peripheral blood stem cell transplantation: Peripheral blood stem cell transplantation is done 14 days after 2nd dose of Samarium is delivered Sm-EDTMP (low dose): Sm-EDTMP (low dose) administered after autologous stem cell collection 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. | 0 | 0 | 0 | 11 | 10 | 11 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Low Platelets | Blood and lymphatic system disorders | CTCAE 3.0 | Systematic Assessment | Grade 3 or 4 |
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| Neutorpenia | Blood and lymphatic system disorders | CTCAE 3.0 | Systematic Assessment | Gr 1-2: 3 subjects Gr 3-4: 5 subjects |
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| Anemia | Blood and lymphatic system disorders | CTCAE 3.0 | Systematic Assessment | Gr 1: 10 subjects |
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| pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE 3.0 | Systematic Assessment | Gr3 increase in size of pleural effusion (disease related). This subject is not evaluable for hematologic recovery. |
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| Hyponatremia | Metabolism and nutrition disorders | CTCAE 3.0 | Systematic Assessment | asymptomatic. Grade 3. Resolved spontaneously. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David M. Loeb, M.D., Ph.D., Director, Musculoskeletal Tumor Program | Sidney Kimmel Comprehensive Cancer Center | 410.502.7247 | loebda@jhmi.edu |
| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D012516 | Osteosarcoma |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018213 | Neoplasms, Bone Tissue |
| D009372 | Neoplasms, Connective Tissue |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| D007069 | Ifosfamide |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| C061972 | samarium Sm-153 lexidronam |
| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D003520 | Cyclophosphamide |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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