Neoplasms

All Conditions

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Osteosarcoma

Sarcoma

Bone Neoplasms

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Analgesics

All Drugs and Chemicals

Samarium Sm-153 lexidronam

Analgesics, Non-Narcotic

DAY 1 Tracer dose 153Sm-EDTMP administration (1 mCi/kg) SPECT/High-resolution CT at 4 hours. SPECT/CT (low resolution) at 24 and 48 hrs

DAY 7 Individualized treatment dose 153Sm-EDTMP administration (max 30 mCi/kg) SPECT scans at 4, 24 and 48 hours

DAY 21 (2 weeks following treatment dose) Auto-Stem cell infusion

DAY 40 (approx. two weeks after stem cell rescue) Initiate EBT upon count recovery

1 MONTH following completion of all therapy Response assessment with repeat imaging (CT/MRI, Tc-99m bone scan) 18F-MISO/FDG PET

Subjects receive a "tracer" infusion of Samarium-153 EDTMP at 1 mCi/kg. 3D dosimetry using SPECT images are obtained post "tracer" infusion to determine the distribution of dose delivered to the tumor and surrounding normal tissues. "Tracer" activity will be applied to development of the external beam radiation (EBT) planning. Second "treatment" infusion of Samarium will then be implemented. Maximum activity administered will be 30 mCi/kg.

Sm-EDTMP

Administered 14 days after "Treatment" infusion of Samarium-153 EDTMP.

Autologous Stem Cell Infusion

The radiotherapy portion of the combined plan will be delivered according to the judgement of the treating radiation oncologist. The total dose to be used will be modified based on surrounding tissue tolerances as evidenced by Samarium infusion and SPECT image planning.

After the "treatment" infusion, SPECT scans will again be performed to confirm the total dose delivered and subsequently adjust the EBT portion of the treatment plan, as necessary.

External Beam Radiotherapy

Brian Ladle, MD, PhD

The primary goal of this study will be to examine tumor response after radiation treatment via a combination of Samarium-153 EDTMP and external beam radiotherapy.

Samarium tracer infusion of 1 mCi/kg administered. SPECT images wil be used to determine the distribution of dose delivered to the tumor. This information will be used to determine target doses of external beam radiotherapy. The treatment infusion of Samarium, 30 mCi/kg, will be administered and dosimetry will confirm total dose delivered, and information will be used to finalize doses of external beam radiotherapy. Approximately 14 days after treatment infusion, autologous stem cells infusion is administered. Radiotherapy will be delivered according to the judgement of the treating radiation oncologist.

Combination of External Beam Radiotherapy With 153Sm-EDTMP to Treat High Risk Osteosarcoma

Percentage of patients with high-risk osteogenic sarcoma, treated with high-dose Samarium-153 EDTMP and external beam radiotherapy, without progression at 6 months.

Number of patients experiencing any Grade 3-4 toxicity, as defined by CTCAE v4.0 and RTOG Cooperative Group Common Toxicity Criteria, during the trial intervention and follow-up.

National Cancer Institute (NCI)

Jazz Pharmaceuticals

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

No patients who enrolled on the trial survived longer than 4 months. Toxicities were graded according to CTCAE v4.0 and the RTOG Cooperative Group Common Toxicity Criteria, and attributable toxicities grade 3 or higher were recorded.

SmEDTMP/Autologous Stem Cell Infusion/RT

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The study had low enrollment - 4 patients. Those that did enroll had very late stage disease and the therapy provided on this trial was the last therapy given for all 4 patients. Of the patients that began therapy, only 1 completed planned therapy.

Dr. Brian H. Ladle

Percentage of Treated Participants With 6-month Progression Free Survival

Samarium tracer infusion of 1 mCi/kg administered. SPECT images wil be used to determine the distribution of dose delivered to the tumor. This information will be used to determine target doses of external beam radiotherapy. The treatment infusion of Samarium, 30 mCi/kg, will be administered and dosimetry will confirm total dose delivered, and information will be used to finalize doses of external beam radiotherapy. Approximately 14 days after treatment infusion, autologous stem cells infusion is administered. Radiotherapy will be delivered according to the judgement of the treating radiation oncologist.

External Beam Radiotherapy: The radiotherapy portion of the combined plan will be delivered according to the judgement of the treating radiation oncologist. The total dose to be used will be modified based on surrounding tissue tolerances as evidenced by Samarium infusion and SPECT image planning.

Short and Long-term Side Effects of Combined Infusional Samarium-153 EDTMP and External Beam Radiotherapy as Assessed by Number of Participants With Toxicity

Samarium tracer infusion of 1 mCi/kg administered. SPECT images wil be used to determine the distribution of dose delivered to the tumor. This information will be used to determine target doses of external beam radiotherapy. The treatment infusion of Samarium, 30 mCi/kg, will be administered and dosimetry will confirm total dose delivered, and information will be used to finalize doses of external beam radiotherapy. Approximately 14 days after treatment infusion, autologous stem cells infusion is administered. Radiotherapy to be delivered according to the judgement of the treating radiation oncologist.

Overall Study

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

Dermatologic Agents

Antibodies

Antibodies, Monoclonal

Carboplatin

Etoposide

Melphalan

Lenograstim

Etoposide phosphate

Immunoglobulins

Isotretinoin

Tretinoin

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Adjuvants, Immunologic

Keratolytic Agents

According to patient weight and renal function, consolidation chemotherapy using various doses of Melphalan, Etoposide, and Carboplatin followed by autologous stem cell infusion and serial post-transplant Granulocyte Colony Stimulating Factor, radiation therapy and Isotretinoin maintenance therapy.

Carboplatin intravenously (IV), 425 mg/m2/dose (or if ≤ 12kg, 14.2 mg/kg/dose) once daily x 4 doses on days 7 through 4 pretransplant.

On day 0 the stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.

Autologous stem cell infusion

Beginning on day 0 after infusion of the PBSC, patients will receive G-CSF subcutaneously (SQ) or IV (SQ preferred) 5 micrograms/kg once daily and continuing once daily until post-nadir absolute neutrophil count (ANC) \> 2000/μL for 3 consecutive days.

Granulocyte colony stimulating factor

It is suggested that patients who have a complete surgical resection of the primary tumor receive 21.6 Gy external beam radiation therapy (EBRT) to the post-induction chemotherapy, pre-operative primary tumor volume. It is suggested that patients who have an incomplete surgical resection of the primary tumor (residual soft tissue mass measuring \>1 cm3) will receive 21.6 Gy EBRT to the postinduction chemotherapy, pre-operative primary tumor volume and an additional boost of 14.4 Gy EBRT to the gross residual tumor (total dose 36 Gy to gross residual tumor volume). Radiation should be given after stem cell transplantation and should start no sooner than 28 days post transplant.

Radiation therapy

Post-transplant maintenance therapy with cis-RA daily for 14 days every 28 days repeated for 6 months. This phase of the therapy can be initiated by the BMT team and continued by the referring physician. It is recommended to begin Isotretinoin at day 66 post-transplant and no later than day 100. For patients ≤12 kg, isotretinoin (accutane) should be administered at 5.33 mg/kg/dose divided twice daily. For patients \>12 kg isotretinoin (accutane) should be administered at 160 mg/m\^2/day divided twice a day. Patients should be considered for monoclonal antibody therapy against GD2, such as ch14.18 if such trials are available.

Isotretinoin (13-cis-retinoic acid)

Melphalan Intravenously (IV), 70 mg/m2/dose (or if ≤ 12 kg, 2.3 mg/kg/dose) once daily x 3 doses on days 7 through 5 pretransplant

Etoposide intravenously (IV), 338 mg/m2/dose (or if ≤ 12kg, 11.3 mg/kg/dose) once daily x 4 doses on days 7 through 4 pretransplant

Ashish Gupta, MBBS, MPH

This is a standard of care document, outlining the therapy for children with high risk neuroblastoma who are not eligible for Children's Oncology Group (COG) studies.

This therapy involves the use of melphalan, etoposide, and carboplatin (consolidation chemotherapy); autologous stem cell rescue, post-transplant radiation therapy and a maintenance phase with Isotretinoin (Accutane, 13-cis-retinoic acid) therapy. If available, patients should also consider post-transplant therapy with cytokines and monoclonal antibody (ch14.18) on a COG or New Approaches to Neuroblastoma Therapy (NANT) trial.

High Dose Chemotherapy and Autologous Transplant for Neuroblastoma

High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell (PBSC) Rescue for Neuroblastoma: Standard of Care Considerations

The time to neutrophil engraftment will be assessed by standard statistical approaches.

The number of patients alive and disease free will be assessed using standard statistical approaches.

The number of patients alive will be assessed by standard statistical approaches.

The rate of treatment related mortality will be assessed by cumulative incidence approach.

Masonic Cancer Center, University of Minnesota

Antirheumatic Agents

Cyclophosphamide

Thiotepa

Consolidation course #1 consists of thiotepa and cyclophosphamide followed by a PBSC rescue. Consolidation course #2 consists of melphalan, etoposide and carboplatin followed by a second PBSC rescue. Post infusion, patients will receive Granulocyte-Colony Stimulating Factor beginning on Day 0 of each consolidation course.

Thiotepa by IV once daily for 3 doses on Days -7, -6 and -5. Given as part of Consolidation Course #1 along with Cyclophosphamide.

Cyclophosphamide by IV once daily for 4 doses on Days -5, -4, -3 and -2. Given as part of Consolidation Course #1 along with Thiotepa.

Melphalan by IV once daily for 3 doses on Days -8, -7, and -6. Given as part of Consolidation Course #2 along with Etoposide and Carboplatin.

Etoposide by IV once daily for 4 doses on Days -8, -7, -6 and -5. Given as part of Consolidation Course #2 along with Melphalan and Carboplatin.

Carboplatin by IV once daily for 4 doses on Days -8, -7, -6 and -5. Given as part of Consolidation Course #2 along with Etoposide and Melphalan.

On Day 0 the stem cells will be infused immediately after thawing over 15-60 minutes per institutional guidelines.

Beginning on day 0 after infusion of the PBSC, patients will receive G-CSF SQ or IV (SQ preferred) 5 micrograms/kg once daily and continuing once daily until post-nadir ANC \> 2000/μL for 3 consecutive days.

Lisa Burke

Lisa Burke, RN

This is a phase II single center study to administer two courses of myeloablative consolidation chemotherapy each followed by an autologous peripheral blood stem cell (PBSC) rescue in patients with high-risk neuroblastoma who have completed induction chemotherapy (independent of this study). Ideally, patients should begin consolidation chemotherapy no later than 8 weeks after the start of Induction Cycle #5; however it is strongly recommended to begin consolidation within 4-6 weeks after the start of Induction Cycle #5.

Myeloablative Consolidation Therapy and Tandem Autologous Stem Cell Rescue in Patients With High-Risk Neuroblastoma

Tandem Myeloablative Consolidation Therapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma

Percentage of patients with progression free survial. Kaplan-Meier curves and 95% confidence intervals will be used to estimate.

Defined as an absolute neutrophil count (ANC) greater than or equal to 0.5 x 109/L for three consecutive days by day 42 after first transplant.

Percentage of patients with relapse. Relapse will be defined as any new lesion; increase of any measurable lesion by \>25%; previous negative bone is positive.

Kaplan-Meier curves and 95% confidence intervals will be used to estimate overall survival.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination of External Beam Radiotherapy With 153Sm-EDTMP to Treat High Risk Osteosarcoma	NCT01886105	Metastatic Oste...	Sm-EDTMP Autologous Stem... External Beam R...	10 Years - 65 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
High Dose Chemotherapy and Autologous Transplant for Neuroblastoma	NCT01526603	Neuroblastoma	Carboplatin Autologous stem... Granulocyte col... Radiation thera... Isotretinoin (1... Melphalan Etoposide	- 30 Years	Masonic Cancer Center, University of Minnesota
Myeloablative Consolidation Therapy and Tandem Autologous Stem Cell Rescue in Patients With High-Risk Neuroblastoma	NCT02605421	Neuroblastoma	Thiotepa Cyclophosphamid... Melphalan Etoposide Carboplatin Autologous Stem... Granulocyte col...	- 30 Years	Masonic Cancer Center, University of Minnesota
High Dose Chemotherapy and Autologous Transplant for Neuroblastoma	NCT01526603	Neuroblastoma	Carboplatin Autologous stem... Granulocyte col... Radiation thera... Isotretinoin (1... Melphalan Etoposide	- 30 Years	Masonic Cancer Center, University of Minnesota

Spots Global Cancer Trial Database for autologous stem cell infusion