Pilot Study Using Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients with Newly Diagnosed High-Risk Neuroblastoma
This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma. Giving chemotherapy to the entire body before a stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is 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.
Inclusion Criteria:Ages Eligible for Study: up to 30 YearsPatients must have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following: MYCN amplification ( greater than 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features Age greater than 18 months ( greater than 547 days) regardless of biologic features Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index equal to 1) or any biologic feature that is indeterminate/unsatisfactory/unknown Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following: MYCN amplification ( greater than 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features Age greater than 18 months ( greater than 547 days) with unfavorable pathology, regardless of MYCN status Patients with newly diagnosed neuroblastoma with INSS stage 2A/2B with MYCN amplification ( greater than 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features Patients with newly diagnosed neuroblastoma with INSS Stage 4S with MYCN amplification ( greater than 4-fold increase in MYCN expression signals as compared to reference signals), regardless of additional biologic features Patients greater than equal to 365 days initially diagnosed with neuroblastoma INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; study enrollment on ANBL12P1 must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S Patients must not have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification status and histology Creatinine clearance or radioisotope glomerular filtration rate (GFR) greater than equal to 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: Age 1 month to less than 6 months: 0.4 mg/dL Age 6 months to less than 1 year: 0.5 mg/dL Age 1 to less than 2 years: 0.6 mg/dL Age 2 to less than 6 years: 0.8 mg/dL Age 6 to less than 10 years: 1 mg/dL Age 10 to less than 13 years: 1.2 mg/dL Age 13 to less than 16 years: 1.5 mg/dL (males), 1.4 mg/dL (females) Age greater than equal to 16 years: 1.7 mg/dL (males), 1.4 mg/dL (females) Total bilirubin equal to less than 1.5 x upper limit of normal (ULN) for age, and Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) less than 10 x ULN for age Shortening fraction of greater than equal to 27% by echocardiogram, or ejection fraction of greater than equal to 50% by radionuclide evaluation No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.Exclusion Criteria: Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA index greater than 1) are not eligible Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events Lactating females are not eligible unless they have agreed not to breastfeed their infants Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation.
This groupwide pilot study examines the toxicity profile of the Busulfan-Melphalan (BuMel) myeloablative preparative regimen in children and young adults with newly diagnosed high-risk neuroblastoma. The primary objective of the proposed study will be to examine the toxicity profile of this regimen in the context of COG therapy, with specific focus on the incidence and severity of pulmonary and hepatic toxicity. The Induction regimen will be 5 cycles of Induction. Consolidation therapy will consist of 4 doses of busulfan IV given once daily followed by a single dose of melphalan with a rest day prior to and following the melphalan dose. After recovery from Consolidation radiation therapy, patients will be encouraged to participate in clinical trials of ch14.18 immunotherapy (ie, ANBL0032 or other).Additional examinations will include pharmacokinetic measurements of busulfan and melphalan that will be collected and correlated with toxicity and survival. We will examine the ability to perform Curie scoring in real time, within 21 days of scan acquisition. This will be the first prospective use of Curie scoring in a cooperative group setting. This study will examine our ability to perform ALK gene testing prospectively, within 4 to 6 weeks of sample acquisition, by a centralized lab. Aberrations of the ALK gene in neuroblastoma tumors have been reported by multiple investigators, with potential therapeutic implications. Potential targeted inhibitors of ALK aberrations are now available, and may impact future clinical trial designs. In addition, molecular profiling of MYCN non-amplified tumors with a 14-gene signature panel will be performed. This study will test our ability to obtain tumor samples prospectively and identify molecular profiles within 6-8 weeks of sample acquisition which may also impact future clinical trial design.
08/28/2014 04:23 AM