NCT00253435

N2001-02: I-MIBG With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma

I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: Children's Hospital Los Angeles · Academic / Other
• Sex: All
• Age: 1 Year – 29 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine, may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as carboplatin, etoposide, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. An autologous peripheral stem cell or bone marrow transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 metaiodobenzylguanidine and combination chemotherapy with an autologous peripheral stem cell or bone marrow transplant may allow more chemotherapy to be given so that more tumor cells are killed. Giving radiation therapy after an autologous peripheral stem cell or bone marrow transplant may kill any remaining tumor cells. PURPOSE: This phase II trial is studying how well giving iodine I 131 metaiodobenzylguanidine together with combination chemotherapy and radiation therapy works in treating patients who are undergoing an autologous peripheral stem cell or bone marrow transplant for relapsed or refractory neuroblastoma.

Detailed description

OBJECTIVES: Primary * Determine the response rate in patients with relapsed or refractory neuroblastoma treated with iodine I 131 metaiodobenzylguanidine (\^131I-MIBG) and combination chemotherapy comprising carboplatin, etoposide, and melphalan followed by autologous bone marrow or peripheral blood stem cell transplantation and radiotherapy. Secondary * Determine the hematopoietic and nonhematopoietic toxicity of this regimen in these patients. * Determine the tumor self-absorbed radiation dose (TSARD) in patients with measurable soft tissue lesions treated with this regimen. * Correlate the TSARD with tumor response in patients with measurable residual soft tissue disease treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to risk (poor-risk group \[mixed or no response to induction therapy or progression during or after induction therapy\] vs good-risk group \[partial response after 4 courses of induction therapy\]) and kidney function at study entry (glomerular filtration rate \[GFR\] ≥ 100 mL/min vs GFR 60-99 mL/min) * Stem cell harvest: Patients undergo a peripheral blood stem cell harvest or bone marrow harvest provided they have an adequate number of cells available. At least 2 weeks later, patients proceed to iodine I 131 metaiodobenzylguanidine (\^131I-MIBG) and combination chemotherapy. * 131I-MIBG and combination chemotherapy: Patients receive \^131I-MIBG IV over 2 hours on day -21, carboplatin IV continuously on days -7 to -4, etoposide IV continuously on days -7 to -4, and melphalan IV over 1 hour on days -7 to -5. * Stem cell infusion and filgrastim (G-CSF): Three days after completion of chemotherapy, patients undergo transplantation of either stem cells or bone marrow on day 0. Patients also receive G-CSF subcutaneously or IV over 1 hour once daily beginning on day 0 and continuing until blood counts return to normal. * Radiotherapy: Once blood counts return to normal, patients undergo radiotherapy to primary and metastatic sites that have not received previous irradiation over 12 days beginning after day 42. After completion of study treatment, patients are followed for 2 years and then periodically thereafter. PROJECTED ACCRUAL: Approximately 50 patients (40 low-risk patients and 8-10 high-risk patients) will be accrued for this study.

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Filgrastim	Filgrastim 5 micrograms/kg/day S.C. or IV will be given daily beginning on Day 0. The first dose should begin four hours after the stem cell infusion is completed. Filgrastim will continue daily until the ANC \>=1500/uL for three consecutive days.
DRUG	Carboplatin	The carboplatin will be administered as a continuous IV infusion Day - 7 through Day - 4, with dosing based upon pretreatment GFR levels. The carboplatin should be diluted to a concentration of 0.3 mg/ml in D5W 0.45NS and infused concomitantly with etoposide through the same central venous catheter using a "Y" connector; a controlled rate infusion pump is used for each arm of the "Y".
DRUG	Etoposide	The etoposide shall be administered day -7 through day -4 via continuous intravenous infusion over 96 hours. For patients with a corrected GFR \>= 100 ml/min/1.72 m\^2, a dose of 300 mg/m\^2/day (10 mg/kg/day if child is \< 12 kg) shall be given. For patients with a corrected GFR 60-99 ml/min/1.72 m\^2, the etoposide will be administered at a dose of 160 mg/m\^2/day (5.3 mg/kg/day). The etoposide will be diluted in D5W 0.45%NS at a concentration of \< 0.4 mg/ml. Etoposide should not be mixed with carboplatin, but administered using a Y-connector.
DRUG	Melphalan	For patients in either the normal GFR strata (\>=100 ml/min/1.73 m\^2), or reduced GFR strata (60-99 ml/min/1.73m\^2), melphalan shall be administered at a dose of 60 mg/m\^2/day (2 mg/kg/day if child is \< 12 kg) on day -7, -6, and -5 of study. The melphalan should be infused at a rate of less than 10 mg/minute, and should complete within 1 hour of reconstitution each day. The melphalan should be diluted in 0.9% NaCl at a concentration \< 2 mg/ml. The total dosage of melphalan to be administered will be 180 mg/m\^2.
PROCEDURE	Peripheral blood stem cell infusion	Stem cells or marrow will be infused on day 0 of study therapy. Where the DMSO concentration in the stem cell product would exceed accepted level for infusion within a 24 hour period, stem cell products may be infused over two days to meet this standard. For purged PBSC: A minimum of 2.0 x 10\^6 viable CD34+ cells/kg must be available. For unpurged PBSC, a minimum of 2.0 x 10\^6 viable CD34+ cells/kg must be available. Having a back-up of 2.0 x 10\^6 viable CD34+ cells/kg purged or unpurged PBSC is recommended but not required. For purged bone marrow, a minimum of 1.5 x10\^8 mononuclear cells/kg must be available.
RADIATION	131I-MIBG	Therapeutic 131I MIBG will be synthesized by Draximage Canada.with specific activity between 15 and 25mCi/ml. Radiopurity will be initially determined by Draximage, prior to shipment to participating centers. Free radioiodide content must then be rechecked at the treating center prior to infusion using HPLC or Sep-Pac methodology.
RADIATION	Radiation therapy	Local irradiation is to be given to previously non-irradiated primary and metastatic sites of disease. Local irradiation should not start till the patient is medically stable, has an ANC \> 1000/uL, platelets \> 30,000 / uL, and is \> 42 days post transplant. Recommended radiation guidelines consist of 2160 cGy total, given over 12 days using a single 180 cGy fraction/day. Any delay in local radiation that would extend treatment beyond day +84 should be discussed with the study chair. Local radiation will be administered at a participating NANT member site.

Timeline

• Start date: 2005-09-01
• Primary completion: 2012-12-01
• Completion: 2013-12-01
• First posted: 2005-11-15
• Last updated: 2023-04-10
• Results posted: 2016-08-24

Locations

15 sites across 2 countries: United States, Canada