New Approaches To Neuroblastoma Therapy Research Articles

Clinical and biologic predictors of response to MIBG therapy: A report from the new approaches to neuroblastoma therapy (NANT) consortium.

e22003 Background: 131I-metaiodobenzylguanidine (MIBG) remains one of the most active agents for neuroblastoma. The clinical and biologic predictors of response to MIBG therapy have not been systematically characterized in a recent era trial. Methods: Patients 1-30 years were enrolled on the randomized phase 2 trial of MIBG vs. MIBG/vincristine/irinotecan vs. MIBG/vorinostat for relapsed/refractory neuroblastoma (NANT2011-01, NCT02035137) between 2014-2019. Data were compared between those who had an objective response (partial response or better using NANT response criteria) to MIBG after the first cycle and those who did not according to clinical features (age at study enrollment; sex; response to prior therapy; prior receipt of MIBG therapy; bone marrow involvement at study enrollment; and measurable disease status at study enrollment) and MYCN status. Univariate analyses were performed using odds ratio and Fisher exact tests. Multivariate logistic regression analysis was used to identify predictors of response to MIBG therapy while controlling for key confounders. Results: 105 response-evaluable patients were included in the analytic cohort. Across the 3 study arms, 20% (21/105) had an objective response to the treatment. Only measurable disease status was statistically significantly associated with response to therapy, with higher rates of response among patients without measurable disease at study enrollment (30% vs. 13%, p = 0.049). Response to prior therapy, sex, MYCN status, and measurable disease status showed univariate odds ratios of 2 or greater (Table). Only measurable disease status remained statistically significant in the multivariate analysis (p = 0.043, Table). Conclusions: Patients without measurable disease have a higher rate of objective responses to MIBG therapy. Understanding these differences based upon predictors of response may help to inform stratification methods for future MIBG clinical trials.[Table: see text]

Phase I study of 131I-MIBG with dinutuximab for patients with relapsed or refractory neuroblastoma: A report from the new approaches to neuroblastoma therapy (NANT) consortium.

10038 Background: 131I-metaiodobenzylguanidine (MIBG) is one of the most active salvage therapies for patients with relapsed or refractory (R/R) high-risk neuroblastoma (HRNB). Preclinical neuroblastoma studies show cooperative effects when radiation is combined with anti-GD2 monoclonal antibody (mAb). We hypothesized that MIBG would synergize with the anti-GD2 mAb dinutuximab to provide improved anti-tumor responses. The primary aims of Part A of this study were to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of MIBG administered with dinutuximab in children with R/R HRNB and to define and describe the toxicities. Methods: Patients 1-29 years of age with R/R HRNB who had MIBG uptake in ≥ 1 site were eligible. Prior anti-GD2 mAb therapy was allowed provided it was not administered with MIBG and not permanently discontinued due to toxicity. One prior MIBG therapy was allowed. MIBG was administered on day 1 at one of three dose levels (DLs): 12, 15, and 18 mCi/kg (DL1-DL3, respectively) with an expansion cohort at the RP2D. Doses were escalated using a rolling six design starting at DL1. The primary endpoint was dose-limiting toxicity (DLT) during course 1. Dinutuximab (17.5 mg/m2/dose) was administered intravenously on days 8-11 and 29-32 and GM-CSF (250 mcg/m2/dose) subcutaneously on days 8-17 and 29-38. Autologous peripheral blood stem cells were infused to all patients on day 15 (+/- 2 days). A maximum of 2 courses per patient were allowed. Response rate was defined as the proportion of patients with a complete or partial response. Results: Thirty-one patients were enrolled. Fourteen were evaluable for dose escalation (4 on DL1, 4 on DL2, and 6 on DL3); 5 evaluable patients were treated in the DL3 expansion. The median age was 7.4 years (range: 3.1 – 22.0) and 20 (65%) were male. Twenty-seven (87%) patients had previously received a median of 8.5 cycles of chemoimmunotherapy (range: 2 – 21). Eight patients previously progressed while receiving anti-GD2 mAb including 7 in DL3. Five (16%) patients had previously received MIBG. No patient at any dose level experienced DLT. Common grade 3/4 treatment-related toxicities were expected hematologic toxicities attributable to MIBG and non-hematologic toxicities attributable to dinutuximab or GM-CSF. Among 26 response-evaluable patients, the centrally-confirmed response rate was 31% across all dose levels: 2/6 (33%) in DL1, 3/5 (60%) in DL2, and 3/15 (20%) in DL3. There were 3 minor responses, 1 in DL2 and 2 in DL3. Conclusions: The RP2D of MIBG in combination with standard doses of dinutuximab and GM-CSF is 18 mCi/kg. This radioimmunotherapy regimen is well-tolerated without additive toxicity. Preliminary efficacy data are encouraging in this heavily pre-treated patient population. A phase 2 trial of this regimen is planned in patients with R/R HRNB. Clinical trial information: NCT03332667.

Phase II study of alisertib, irinotecan, and temozolomide in children with relapsed and refractory neuroblastoma: A report from the New Approaches to Neuroblastoma Therapy (NANT) consortium.

10556Background: In phase I testing in 22 patients with neuroblastoma, the maximum tolerated dose of alisertib tablets with irinotecan/temozolomide was 60 mg/m2/dose. This combination showed signif...

131I-Metaiodobenzylguanidine with Intensive Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Neuroblastoma. A New Approaches to Neuroblastoma Therapy (NANT) Phase II Study

131I-Metaiodobenzylguanidine (131I-MIBG) has been used as a single agent or in combination with chemotherapy for the treatment of high-risk neuroblastoma. The activity and toxicity of 131I-MIBG when combined with carboplatin, etoposide, and melphalan (CEM) and autologous stem cell transplantation (SCT) are now investigated in a phase II multicenter study. Fifty patients with MIBG-avid disease were enrolled into 2 cohorts, stratified by response to induction therapy. The primary study endpoint was response of patients with refractory (n = 27) or progressive disease (n = 15). A second cohort of patients (n = 8) with a partial response (PR) to induction therapy was included to obtain preliminary response data. 131I-MIBG was administered on day -21 to all patients, with CEM given days -7 to -4, and SCT given on day 0. 131I-MIBG dosing was determined by pre-therapy glomerular filtration rate (GFR), with 8 mCi/kg given if GFR was 60 to 99 mL/minute/1.73 m2 (n = 13) and 12 mCi/kg if GFR ≥ 100 mL/minute/1.73 m2 (n = 37). External beam radiotherapy was delivered to the primary and metastatic sites, beginning approximately 6 weeks after SCT. Responses (complete response + PR) were seen in 4 of 41 (10%) evaluable patients with primary refractory or progressive disease. At 3 years after SCT, the event-free survival (EFS) was 20% ± 7%, with overall survival (OS) 62% ± 8% for this cohort of patients. Responses were noted in 3 of 8 (38%) of patients with a PR to induction, with 3-year EFS 38% ± 17% and OS 75% ± 15%. No statistically significant difference was found comparing EFS or OS based upon pre-therapy GFR or disease cohort. Six of 50 patients had nonhematologic dose-limiting toxicity (DLT); 1 of 13 in the low GFR and 5 of 37 in the normal GFR cohorts. Hepatic sinusoidal obstructive syndrome (SOS) was seen in 6 patients (12%), with 5 events defined as dose-limiting SOS. The median times to neutrophil and platelet engraftment were 10 and 15 days, respectively. Patients received a median 163 cGy (61 to 846 cGy) with 131I-MIBG administration, with 2 of 3 patients receiving >500 cGy experiencing DLT. The addition of 131I-MIBG to a myeloablative CEM regimen is tolerable and active therapy for patients with high-risk neuroblastoma.

Phase I trial of fenretinide delivered orally in a novel organized lipid complex in patients with relapsed/refractory neuroblastoma: A report from the new approaches to neuroblastoma therapy (NANT) consortium

A phase I study was conducted to determine the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics of fenretinide (4-HPR) delivered in an oral powderized lipid complex (LXS) in patients with relapsed/refractory neuroblastoma. 4-HPR/LXS powder (352-2,210 mg/m(2) /day) was administered on Days 0-6, in 21-day courses, by standard 3 + 3 design. Thirty-two patients (median age = 8 years, range 3-27 years) enrolled with 30 evaluable for dose escalation. Prior therapies included stem cell transplantation/support (n = 26), 13-cis-retinoic acid (n = 22), (125/131) I-MIBG (n = 13), and anti-GD2 antibody (n = 6). 170+ courses were delivered. Course 1 DLTs were a Grade 3 (n = 1) alkaline phosphatase at 352 mg/m(2) /day. Other major toxicities were Grade 4 (n = 1) alkaline phosphatases on Courses 5 and 6 at 774 mg/m(2) /day, and Grade 3 (n = 1) ALT/AST elevation on Course 2 at 1,700 mg/m(2) /day. Of 29 response-evaluable patients, six had stable disease (SD) (4-26 courses); four with marrow- or bone disease-only had complete responses (CR) (10-46 courses). 4-HPR plasma levels were several folds higher (P < 0.05) than previously reported using capsular fenretinide. The Day 6 mean peak 4-HPR plasma level at 1,700 mg/m(2) /day was 21 µM. An MTD was not reached. 4-HPR/LXS oral powder obtained higher plasma levels, with minimal toxicity and evidence of anti-tumor activity, than a previous capsule formulation. A recommended phase II schedule of 4-HPR/LXS powder is 1,500 mg/m(2) /day, TID, on Days 0-6, of a 21-day course.

Comparison of Taqman low density array (TLDA) five-gene assay for tumor cells in bone marrow and blood with histologic bone marrow examination and imaging for disease assessment and outcome in patients with recurrent/refractory neuroblastoma (NBL): A new approaches to neuroblastoma therapy (NANT) study.

10039 Background: Accurate quantification of tumor burden in NBL patients is needed to define homogenous populations for therapy and establish response criteria that predict outcome. The 5-gene TLDA assay was developed for quantification of NBL cells in bone marrow (BM) and blood (BLD). Methods: Expression of CHGA, DCX, DDC, PHOX2B, and TH (NBL genes) was quantified with TLDA and reported as the geometric mean cycle threshold for the 5 genes (DGS=detection gene score; inversely related to tumor content, 40=negative). Sixty-three patients with recurrent/refractory NBL had TLDA performed on 107 BM and 99 BLD samples (66 paired) at 140 time points. Based on central review of reports, tumor longest diameter (LD) on CT/MRI (n=118), and number of 123I-MIBG avid sites (n=120) were recorded. Percentage of tumor cells in BM was from institutional reports of bilateral BM aspirates/biopsies (n=109). Overall response was assessed per NANT Response Criteria. Spearman rank correlation was performed. Results:TLDA detected tumor cells in 62/99(63%) BLD (average DGS=37.45) and 91/107(85%) BM samples (average DGS=33.42). 39/91(42%) with positive BM TLDA were negative by morphology. BLD and BM TLDA were correlated r = 0.6540, p&lt; 0.0001 with stronger correlation with lower BM DGS scores. The BM and BLD DGS correlated with % BM involvement (BM r= -0.63, p&lt;0.0001; BLD r= -0.35, p=0.0023) and number of MIBG sites (BM r=-0.34, p=0.001, BLD r=-0.51 p&lt;0.0001) but not LD. Number of MIBG sites was also correlated with % BM involvement (r= 0.45, p&lt;0.001) and LD (r= 0.28, p=0.0039). Analysis of 43 BM pairs demonstrated decreasing DGS correlated with overall progressive disease (r= 0.39, p=0.01). Conclusions: This TLDA assay detects NBL cells in both BM and BLD at high rates, and frequently detects tumor cells when BM morphology is negative. Quantification of tumor with DGS correlates with % BM involvement and number MIBG sites. TLDA may provide an additional parameter to delineate response in NBL. Clinical trial information: NCT01587300.

Abstract CN04-03: Development of NSAID eflornithine combinations for treating cancer risk factors

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDS) have been found to be potent inhibitors of carcinogenesis in both preclinical models and in randomized controlled prospective clinical trials in humans. NSAIDS exert their anti-carcinogenic effects by inhibiting cyclooxygenases (COXs) involved in arachidonic acid metabolism and by COX-independent mechanisms. Empirical data indicates eflornithine (difluoromethylornithine or DFMO), an enzyme-activated inhibitor of ornithine decarboxylase (ODC) (Meyskens and Gerner, 1999), is one of the most potent agents known acting in combination with NSAIDS to inhibit carcinogenesis in rodent models (Steele and Lubet, 2010). At least part of the rationale for combining NSAIDS with eflornithine for inhibition of carcinogenesis is that eflornithine inhibits the activity of ODC, the first enzyme in polyamine synthesis, while NSAIDS activate the spermidine/spermine acetyltransferase (SAT1), which targets polyamines for export by specific solute carrier transporters (Gerner and Meyskens, 2009). Thus, NSAIDS and eflornithine both reduce tissue levels of the growth-associated polyamines, but by complementary mechanisms. A clinical trial of the combination of eflornithine and the NSAID sulindac showed dramatic treatment-associated reductions of metachronous colorectal adenomas in patients with prior sporadic colorectal polyps (Meyskens et al., 2008). Several clinical trials in progress or soon to commence will further test the hypothesis that NSAID eflornithine combinations can successfully treat cancer risk factors in patients with specific cancers, or risk of cancer. One group of clinical trials involves patients with neuroblastoma (NB). Patients with poor prognosis NB often have tumors in which MYCN is overexpressed. Preclinical data indicates that MYCN as well as c-MYC drive expression of ODC and other genes in the polyamine pathway, and that inhibiting this pathway with eflornithine suppressed carcinogenesis in mouse models of NB (Hogarty et al., 2008). Likewise, COX-2 is expressed in NB tumors and cell lines, and COX-2 inhibitors such as celecoxib can suppress the growth of NB xenografts (Ponthan et al., 2007). The Neuroblastoma and Medulloblastoma Translational Research Consortium (NMTRC) and the New Approaches to Neuroblastoma Therapy (NANT) group are conducting clinical trials to evaluate the safety and efficacy of eflornithine alone or in combination with NSAIDS and other agents in patients with high risk NB. The NMTRC is conducting an especially novel prevention trial of eflornithine in patients with high risk NB in remission (NCT01586260). Eflornithine NSAID combinations are also being evaluated in other MYC-associated diseases. Familial adenomatous polyposis (FAP) is a genetic syndrome associated with increased risk of colon cancer and other neoplasia and is caused by mutation/deletions in the adenomatous polyposis coli (APC) tumor suppressor gene. MYC mediates intestinal tumorigenesis (Ignatenko et al., 2006) and combinations of eflornithine and NSAIDS are potent inhibitors of intestinal carcinogenesis (Ignatenko et al., 2008) in murine models of FAP. Notable is the change in clinical management of FAP patients over the past two decades. FAP is now managed primarily by surgery, with duodenal polyposis and desmoid disease constituting two current significant clinical problems. An international consortium will be evaluating the combination of eflornithine and sulindac in adult patients with FAP, using time to FAP-related events as the primary outcome (NCT01483144). This same combination will be evaluated in patients with prior sporadic colon cancer in a study to be conducted by a national cooperative group (S0820, Adenoma and second primary prevention trial, NCT01349881) (Rial et al., 2012). These and other trials have been designed to include assessment of a range of biological correlates, including genetic (Zell et al., 2010), tissue (Thompson et al., 2010) and urinary markers (Hiramatsu et al., 2005) of disease prognosis and prediction of treatment responses, including therapy-associated toxicities. Citation Format: Eugene W. Gerner. Development of NSAID eflornithine combinations for treating cancer risk factors. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN04-03.

A phase I study of zoledronic acid and low‐dose cyclophosphamide in recurrent/refractory neuroblastoma: A new approaches to neuroblastoma therapy (NANT) study

Zoledronic acid, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone is a common metastatic site of advanced neuroblastoma. We previously reported efficacy of zoledronic acid in a murine model of neuroblastoma bone invasion prompting this Phase I trial of zoledronic acid with cyclophosphamide in children with neuroblastoma and bone metastases. The primary objective was to determine recommended dosing of zoledronic acid for future trials. Escalating doses of intravenous zoledronic acid were given every 28 days with oral metronomic cyclophosphamide (25 mg/m(2)/day). Toxicity, response, zoledronic acid pharmacokinetics, bone turnover markers, serum IL-6, and sIL-6R were evaluated. Twenty-one patients, median age 7.5 (range 0.8-25.6) years were treated with 2 mg/m(2) (n = 4), 3 mg/m(2) (n = 3), or 4 mg/m(2) (n = 14) zoledronic acid. Fourteen patients were evaluable for dose escalation. A median of one (range 1-18) courses was given. Two dose limiting toxicities (grade 3 hypophosphatemia) occurred at 4 mg/m(2) zoledronic acid. Other grades 3-4 toxicities included hypocalcemia (n = 2), elevated transaminases (n = 1), neutropenia (n = 2), anemia (n = 1), lymphopenia (n = 1), and hypokalemia (n = 1). Osteosclerosis contributed to fractures in one patient after 18 courses. Responses in evaluable patients included 1 partial response, 9 stable disease (median 4.5 courses, range 3-18), and 10 progressions. Zoledronic acid pharmacokinetics were similar to adults. Markers of osteoclast activity and serum IL-6 levels decreased with therapy. Zoledronic acid with metronomic cyclophosphamide is well tolerated with clinical and biologic responses in recurrent/refractory neuroblastoma. The recommended dose of zoledronic acid is 4 mg/m(2) every 28 days.

Phase I study of fenretinide (4-HPR) oral powder in patients with recurrent or resistant neuroblastoma: New Approaches to Neuroblastoma Therapy (NANT) Consortium trial

10009 Background: Fenretinide (4-HPR), a cytotoxic retinoid, achieved limited and variable plasma levels when tested in a corn oil-based capsule. 4HPR/Lym-X-Sorb (LXS) oral powder is a new formulation intended to increase bioavailability, especially in children. Methods: This trial sought to define the toxicities, dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and pharmacokinetics of 4-HPR/LXS oral powder when given mixed in Slim-Fast nutritional shakes, twice a day for 7 days, every 21 days. Eligible patients had high-risk neuroblastoma with recurrent/progressive disease, or disease refractory or persistent after frontline therapy. Dose escalation was in 30% increments using the traditional 3 + 3 design. Plasma levels were measured by HPLC. Results: Thirty-two patients accrued to 8 Dose Levels (DL) (352 –2210 mg/m2/day); 30 patients were evaluable. No MTD was identified. There was a DLT elevation of alkaline phosphatase on DL1. No other DLT's were observed. Other toxicities included dry skin, elevated triglycerides, reversible nyctalopia, and transient transaminase elevation. Course 1 day 7 peak 4HPR plasma levels (Dose (mg/m2/day) - mean, (range)) were: 352 –6 μM (3.8–9.6); 458–11.5 μM (9.7–14.9); 595–17.6 μM (6–24.3); 774–15 μM (9.1–25.3); 1006–6.7 μM (5.2–9.2); 1308–13.9 μM (2.9–23.8); 1700–19.7 μM (17.3–24.3); and 2210–10.8 μM (4–16.5). Course 2 day 7 peak plasma levels trended higher than course 1 at DL5–8. Three patients with isolated bone marrow disease and one with MIBG avid bone lesions, had complete responses (DL4, DL4, DL7, DL8) receiving 10, 17, 18 and 10 courses of therapy, respectively. Six patients had stable disease for 4–27 courses (median 5.5) (DL3, DL4, DL4, DL5, DL6, DL8). Twenty patients had progressive disease. Central review of responses is pending. Conclusions: 4-HPR/LXS oral powder was well tolerated, obtained 2 - 5 fold higher 4HPR plasma levels than fenretinide capsules on the same dose and schedule (P &lt; 0.01), and showed anti-tumor activity (complete responses in 4/15 patients at DL4–8). Based on pharmacokinetic data, a recommended Phase II dose and schedule is 1700 mg/m2/day × 7days every 3 weeks. No significant financial relationships to disclose.

A phase I study of zoledronic acid (ZA) and low-dose cyclophosphamide (CTX) in children with recurrent/refractory neuroblastoma (NB): A New Approaches to Neuroblastoma Therapy (NANT) study

10022 Background: ZA, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone metastases occur in 60% of children with advanced NB. A xenograft mouse model demonstrated ZA with low dose chemotherapy delayed progression of NB bone lesions prompting a phase I trial of ZA. Methods: Three dose levels of intravenous ZA (2, 3, or 4 mg/m2) administered every 28 days were evaluated with continuous daily oral CTX (25 mg/m2/day) in patients with recurrent/refractory NB and bone metastases. The primary objective was to determine a recommended dose of ZA for future trials. PKs with the first dose of ZA and serial serum IL-6 levels (stimulator of osteoclast activity) were evaluated. Results: 21 patients (14 male), median age 7.9 years (0.8–26.6 years), were enrolled at ZA dose levels 2 mg/m2 (n=4), 3 mg/m2 (n=3), and 4 mg/m2 (n=13). Seventy-five cycles were administered with median of 1 cycle per patient (range 1–18). Two DLT (Gr 3 hypophosphatemia) occurred at 4 mg/m2 ZA. Other Gr 3 or 4 toxicities included hypocalcemia (n = 2), elevated transaminases (n = 2), neutropenia (n = 2), anemia (n = 1), lymphopenia (n = 1), and hypokalemia (n = 1). A fracture related to osteosclerosis occurred after 18 cycles. There were no renal or dental complications. There was 1 complete response, 9 stable disease median 4.5 cycles (range 3–18), and 10 progressions (central review pending). At 4 mg/m2, mean serum IL-6 levels decreased from 3.9 pg/mL (95% CI: 2.8–5.2 pg/mL) (n = 11) to 2.9 pg/mL (95% CI: 1.8–4.4 pg/mL) after cycle 1 (n = 8). ZA PK were similar to adults. Conclusions: ZA with low dose CTX is well tolerated with evidence of clinical benefit in children with recurrent/refractory NB. The recommended ZA dose for future study is 4 mg/m2 every 28 days. No significant financial relationships to disclose.

A phase I study of zoledronic acid and low dose cyclophosphamide in children with recurrent/refractory neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) study

9572 Background: Zoledronic acid (ZA), is a new generation, highly potent bisphosphonate that delays progression of bone metastases in adult malignancies. Bone metastases occur in 60% of children with advanced neuroblastoma. Pre-clinical studies demonstrated ZA with low dose chemotherapy delayed progression of osteolytic neuroblastoma lesions in a xenograft mouse model, prompting a phase I trial of ZA in neuroblastoma. Methods: Three dose levels of intravenous ZA (2, 3 or 4 mg/m2) administered every 28 days were evaluated in combination with continuous daily oral cyclophosphamide (CTX) (25 mg/m2/day) in patients with recurrent/refractory neuroblastoma and cortical bone lesions. The primary objective was to determine a recommended dose of ZA for future trials. Serial blood and urine samples were collected for pharmacokinetics, markers of osteoclast activity, and immunologic assays. Results: 14 patients (9 male), median age 7.9 years (0.8 - 26.6 years), were enrolled at ZA dose levels 2 mg/m2 (n=4), 3 mg/m2 (n=3), and 4 mg/m2 (n=7). To date, 13 patients are evaluable for toxicity. Thirty-nine cycles were administered with a median of 1 cycle per patient (range 1 - 12). Treatment was well tolerated; one DLT (Grade 3 hypophosphatemia) occurred at 4 mg/m2 ZA. Other grade 3 or 4 toxicities attributable to the combination included hypocalcemia (n=2), elevated transaminases (n=2), neutropenia (n=2), anemia (n=1), lymphopenia (n=1), and hypokalemia (n=1). Hypocalcemia occurred in 69% of first cycles and 8% of subsequent cycles. There were no renal toxicities or dental complications. There have been 2 partial responses by MIBG (central review pending), 4 stable disease, and 7 progressive disease; one patient is too early for response. Pharmacokinetic and correlative biology study results are pending. Conclusions: ZA is well tolerated and had evidence of responses when given with low dose CTX to children with recurrent/refractory neuroblastoma. The recommended dose of ZA for subsequent study is 4 mg/m2. Future studies incorporating ZA into the regimen for children with NB and cortical bone lesions are planned. No significant financial relationships to disclose.

131I-MIBG with myeloablative chemotherapy for neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) phase I study

8505 Background: To determine the maximum tolerated dose (MTD) and toxicity of 131I-MIBG with CEM (carboplatin, etoposide, melphalan) and autologous transplant (AT). Methods: 24 children age 1.5–16...