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Arlene Naranjo - One of the best experts on this subject based on the ideXlab platform.

  • Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2021
    Co-Authors: Andrew L. Gilman, M. F. Ozkaynak, Arlene Naranjo, Wendy B. London, Mitchell B. Diccianni, Jacek Gan, Jacquelyn A. Hank, Ayse Batova, Sheena C Tenney
    Abstract:

    Purpose: Previously our randomized Phase III trial demonstrated that immunotherapy including Dinutuximab, a chimeric anti-GD2 monoclonal antibody, granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin-2 (IL2) improved survival for children with high-risk neuroblastoma that had responded to induction and consolidation therapy. These results served as the basis for FDA approval of Dinutuximab. We now present long-term follow-up results and evaluation of predictive biomarkers. Experimental Design: Patients recieved 6 cycles of isotretinoin with or without 5 cycles of immunotherapy which consists of Dinutuximab with GM-CSF alternating with IL2. Accrual was discontinued early due to meeting the protocol-defined stopping rule for efficacy, as assessed by 2-year event-free survival (EFS). Plasma levels of Dinutuximab, soluble IL2 receptor (sIL2R) and human anti-chimeric antibody (HACA) were assessed by ELISA. Fcg receptor 2A and 3A genotypes were determined by PCR and direct sequencing. Results: For 226 eligible randomized patients, 5-year EFS was 56.6{plus minus}4.7% for patients randomized to immunotherapy (n=114) versus 46.1{plus minus}5.1% for those randomized to isotretinoin only (n=112) (p=0.042). Five-year overall survival (OS) was 73.2{plus minus}4.2% versus 56.6{plus minus}5.1% for immunotherapy and isotretinoin only patients, respectively (p=0.045). Thirteen of 122 patients receiving Dinutuximab developed HACA. Plasma levels of Dinutuximab, HACA, and sIL2R did not correlate with EFS/OS, or clinically significant toxicity. Fcg receptor 2A and 3A genotypes did not correlate with EFS/OS. Conclusions: Immunotherapy with Dinutuximab improved outcome for patients with high-risk neuroblastoma. Early stoppage for efficacy resulted in a smaller sample size than originally planned, yet clinically significant long-term differences in survival were observed.

  • long term follow up of a phase iii study of ch14 18 Dinutuximab cytokine immunotherapy in children with high risk neuroblastoma cog study anbl0032
    Clinical Cancer Research, 2021
    Co-Authors: Andrew L. Gilman, M. F. Ozkaynak, Arlene Naranjo, Wendy B. London, Sheena C Tenney, Mitchell B. Diccianni, Jacek Gan, Jacquelyn A. Hank, Ayse Batova, Malcolm A. Smith
    Abstract:

    Purpose: Previously our randomized Phase III trial demonstrated that immunotherapy including Dinutuximab, a chimeric anti-GD2 monoclonal antibody, granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin-2 (IL2) improved survival for children with high-risk neuroblastoma that had responded to induction and consolidation therapy. These results served as the basis for FDA approval of Dinutuximab. We now present long-term follow-up results and evaluation of predictive biomarkers. Experimental Design: Patients recieved 6 cycles of isotretinoin with or without 5 cycles of immunotherapy which consists of Dinutuximab with GM-CSF alternating with IL2. Accrual was discontinued early due to meeting the protocol-defined stopping rule for efficacy, as assessed by 2-year event-free survival (EFS). Plasma levels of Dinutuximab, soluble IL2 receptor (sIL2R) and human anti-chimeric antibody (HACA) were assessed by ELISA. Fcg receptor 2A and 3A genotypes were determined by PCR and direct sequencing. Results: For 226 eligible randomized patients, 5-year EFS was 56.6{plus minus}4.7% for patients randomized to immunotherapy (n=114) versus 46.1{plus minus}5.1% for those randomized to isotretinoin only (n=112) (p=0.042). Five-year overall survival (OS) was 73.2{plus minus}4.2% versus 56.6{plus minus}5.1% for immunotherapy and isotretinoin only patients, respectively (p=0.045). Thirteen of 122 patients receiving Dinutuximab developed HACA. Plasma levels of Dinutuximab, HACA, and sIL2R did not correlate with EFS/OS, or clinically significant toxicity. Fcg receptor 2A and 3A genotypes did not correlate with EFS/OS. Conclusions: Immunotherapy with Dinutuximab improved outcome for patients with high-risk neuroblastoma. Early stoppage for efficacy resulted in a smaller sample size than originally planned, yet clinically significant long-term differences in survival were observed.

  • Outcomes and toxicities in patients (pts) non-randomly assigned to immunotherapy Children’s Oncology Group (COG) ANBL0032.
    Journal of Clinical Oncology, 2020
    Co-Authors: Ami V. Desai, Andrew L. Gilman, M. F. Ozkaynak, Arlene Naranjo, Wendy B. London, Sheena C Tenney, Malcolm A. Smith, Nita L. Seibel, Hiroyuki Shimada, Katherine K. Matthay
    Abstract:

    10523Background: Immunotherapy with the anti-GD2 antibody Dinutuximab plus sargramostim (GM-CSF), aldesleukin (IL-2) and isotretinoin following consolidation therapy improved outcome for high-risk ...

  • irinotecan temozolomide and Dinutuximab with gm csf in children with refractory or relapsed neuroblastoma a report from the children s oncology group
    Journal of Clinical Oncology, 2020
    Co-Authors: Rajen Mody, Arlene Naranjo, Wendy B. London, Mitchell B. Diccianni, Jacquelyn A. Hank, Barry L Shulkin, Marguerite T Parisi, Sabah Servaes, Fan F Zhang, Mildred Felder
    Abstract:

    PURPOSEThe combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neur...

  • abstract lb 300 natural antibodies to non human glycans neu5gc and alpha gal correlate with outcome of high risk neuroblastoma patients treated with Dinutuximab on cog anbl0032 and anbl0931
    Cancer Research, 2018
    Co-Authors: Mitchell B. Diccianni, Andrew L. Gilman, Arlene Naranjo, Wendy B. London, Paul M. Sondel, Jenna Mielke, Richard Williams, Karen Messer, Fevzi Ozkaynak, Julie Park
    Abstract:

    Immunotherapy with ch14.18 (Dinutuximab) has significantly improved the survival of high-risk neuroblastoma patients, though late relapses and allergic reaction remain concerning. N-glycolylneuraminic acid (Neu5Gc) and galactose alpha-1,3-galactose (α-gal) are glycans present in most mammals except human. Humans have circulating antibodies against these glycans due to their presence in dairy products and red meats. We investigated whether anti-glycan antibodies influence efficacy or allergic reactions associated with Dinutuximab. Using ELISA, we measured anti-Neu5Gc and anti-α-gal IgG and IgE levels in plasma collected from courses 1 (days -1 & 6), 4 (days 80 & 90) & 5 (days 111 & 118) of patients on two immunotherapy trials of neuroblastoma (ANBL0032 n= 219; ANBL0931 n=100). Levels of IgG and IgE antibodies against both glycans were highest at pretreatment, decreasing significantly over the entire course of therapy as well as within each course of therapy (p Citation Format: Mitchell B. Diccianni, Jenna Mielke, Richard Williams, Karen Messer, Fevzi Ozkaynak, Andrew L. Gilman, Arlene Naranjo, Wendy London, Paul M. Sondel, Julie Park, Alice L. Yu, Childrens Oncology Group. Natural antibodies to non-human glycans Neu5Gc and alpha-gal correlate with outcome of high-risk neuroblastoma patients treated with Dinutuximab on COG ANBL0032 and ANBL0931 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-300.

Wendy B. London - One of the best experts on this subject based on the ideXlab platform.

  • Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2021
    Co-Authors: Andrew L. Gilman, M. F. Ozkaynak, Arlene Naranjo, Wendy B. London, Mitchell B. Diccianni, Jacek Gan, Jacquelyn A. Hank, Ayse Batova, Sheena C Tenney
    Abstract:

    Purpose: Previously our randomized Phase III trial demonstrated that immunotherapy including Dinutuximab, a chimeric anti-GD2 monoclonal antibody, granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin-2 (IL2) improved survival for children with high-risk neuroblastoma that had responded to induction and consolidation therapy. These results served as the basis for FDA approval of Dinutuximab. We now present long-term follow-up results and evaluation of predictive biomarkers. Experimental Design: Patients recieved 6 cycles of isotretinoin with or without 5 cycles of immunotherapy which consists of Dinutuximab with GM-CSF alternating with IL2. Accrual was discontinued early due to meeting the protocol-defined stopping rule for efficacy, as assessed by 2-year event-free survival (EFS). Plasma levels of Dinutuximab, soluble IL2 receptor (sIL2R) and human anti-chimeric antibody (HACA) were assessed by ELISA. Fcg receptor 2A and 3A genotypes were determined by PCR and direct sequencing. Results: For 226 eligible randomized patients, 5-year EFS was 56.6{plus minus}4.7% for patients randomized to immunotherapy (n=114) versus 46.1{plus minus}5.1% for those randomized to isotretinoin only (n=112) (p=0.042). Five-year overall survival (OS) was 73.2{plus minus}4.2% versus 56.6{plus minus}5.1% for immunotherapy and isotretinoin only patients, respectively (p=0.045). Thirteen of 122 patients receiving Dinutuximab developed HACA. Plasma levels of Dinutuximab, HACA, and sIL2R did not correlate with EFS/OS, or clinically significant toxicity. Fcg receptor 2A and 3A genotypes did not correlate with EFS/OS. Conclusions: Immunotherapy with Dinutuximab improved outcome for patients with high-risk neuroblastoma. Early stoppage for efficacy resulted in a smaller sample size than originally planned, yet clinically significant long-term differences in survival were observed.

  • long term follow up of a phase iii study of ch14 18 Dinutuximab cytokine immunotherapy in children with high risk neuroblastoma cog study anbl0032
    Clinical Cancer Research, 2021
    Co-Authors: Andrew L. Gilman, M. F. Ozkaynak, Arlene Naranjo, Wendy B. London, Sheena C Tenney, Mitchell B. Diccianni, Jacek Gan, Jacquelyn A. Hank, Ayse Batova, Malcolm A. Smith
    Abstract:

    Purpose: Previously our randomized Phase III trial demonstrated that immunotherapy including Dinutuximab, a chimeric anti-GD2 monoclonal antibody, granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin-2 (IL2) improved survival for children with high-risk neuroblastoma that had responded to induction and consolidation therapy. These results served as the basis for FDA approval of Dinutuximab. We now present long-term follow-up results and evaluation of predictive biomarkers. Experimental Design: Patients recieved 6 cycles of isotretinoin with or without 5 cycles of immunotherapy which consists of Dinutuximab with GM-CSF alternating with IL2. Accrual was discontinued early due to meeting the protocol-defined stopping rule for efficacy, as assessed by 2-year event-free survival (EFS). Plasma levels of Dinutuximab, soluble IL2 receptor (sIL2R) and human anti-chimeric antibody (HACA) were assessed by ELISA. Fcg receptor 2A and 3A genotypes were determined by PCR and direct sequencing. Results: For 226 eligible randomized patients, 5-year EFS was 56.6{plus minus}4.7% for patients randomized to immunotherapy (n=114) versus 46.1{plus minus}5.1% for those randomized to isotretinoin only (n=112) (p=0.042). Five-year overall survival (OS) was 73.2{plus minus}4.2% versus 56.6{plus minus}5.1% for immunotherapy and isotretinoin only patients, respectively (p=0.045). Thirteen of 122 patients receiving Dinutuximab developed HACA. Plasma levels of Dinutuximab, HACA, and sIL2R did not correlate with EFS/OS, or clinically significant toxicity. Fcg receptor 2A and 3A genotypes did not correlate with EFS/OS. Conclusions: Immunotherapy with Dinutuximab improved outcome for patients with high-risk neuroblastoma. Early stoppage for efficacy resulted in a smaller sample size than originally planned, yet clinically significant long-term differences in survival were observed.

  • Outcomes and toxicities in patients (pts) non-randomly assigned to immunotherapy Children’s Oncology Group (COG) ANBL0032.
    Journal of Clinical Oncology, 2020
    Co-Authors: Ami V. Desai, Andrew L. Gilman, M. F. Ozkaynak, Arlene Naranjo, Wendy B. London, Sheena C Tenney, Malcolm A. Smith, Nita L. Seibel, Hiroyuki Shimada, Katherine K. Matthay
    Abstract:

    10523Background: Immunotherapy with the anti-GD2 antibody Dinutuximab plus sargramostim (GM-CSF), aldesleukin (IL-2) and isotretinoin following consolidation therapy improved outcome for high-risk ...

  • irinotecan temozolomide and Dinutuximab with gm csf in children with refractory or relapsed neuroblastoma a report from the children s oncology group
    Journal of Clinical Oncology, 2020
    Co-Authors: Rajen Mody, Arlene Naranjo, Wendy B. London, Mitchell B. Diccianni, Jacquelyn A. Hank, Barry L Shulkin, Marguerite T Parisi, Sabah Servaes, Fan F Zhang, Mildred Felder
    Abstract:

    PURPOSEThe combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neur...

  • abstract lb 300 natural antibodies to non human glycans neu5gc and alpha gal correlate with outcome of high risk neuroblastoma patients treated with Dinutuximab on cog anbl0032 and anbl0931
    Cancer Research, 2018
    Co-Authors: Mitchell B. Diccianni, Andrew L. Gilman, Arlene Naranjo, Wendy B. London, Paul M. Sondel, Jenna Mielke, Richard Williams, Karen Messer, Fevzi Ozkaynak, Julie Park
    Abstract:

    Immunotherapy with ch14.18 (Dinutuximab) has significantly improved the survival of high-risk neuroblastoma patients, though late relapses and allergic reaction remain concerning. N-glycolylneuraminic acid (Neu5Gc) and galactose alpha-1,3-galactose (α-gal) are glycans present in most mammals except human. Humans have circulating antibodies against these glycans due to their presence in dairy products and red meats. We investigated whether anti-glycan antibodies influence efficacy or allergic reactions associated with Dinutuximab. Using ELISA, we measured anti-Neu5Gc and anti-α-gal IgG and IgE levels in plasma collected from courses 1 (days -1 & 6), 4 (days 80 & 90) & 5 (days 111 & 118) of patients on two immunotherapy trials of neuroblastoma (ANBL0032 n= 219; ANBL0931 n=100). Levels of IgG and IgE antibodies against both glycans were highest at pretreatment, decreasing significantly over the entire course of therapy as well as within each course of therapy (p Citation Format: Mitchell B. Diccianni, Jenna Mielke, Richard Williams, Karen Messer, Fevzi Ozkaynak, Andrew L. Gilman, Arlene Naranjo, Wendy London, Paul M. Sondel, Julie Park, Alice L. Yu, Childrens Oncology Group. Natural antibodies to non-human glycans Neu5Gc and alpha-gal correlate with outcome of high-risk neuroblastoma patients treated with Dinutuximab on COG ANBL0032 and ANBL0931 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-300.

Genevieve Laureys - One of the best experts on this subject based on the ideXlab platform.

Rajen Mody - One of the best experts on this subject based on the ideXlab platform.

  • abstract 2045 characterization of inpatient opioid use among pediatric neuroblastoma patients during Dinutuximab therapy
    Cancer Research, 2020
    Co-Authors: Jola Mehmeti, Jae Eun Choi, Ian Wolfe, Juan P Cata, Rajen Mody
    Abstract:

    Background: Dinutuximab is a chimeric anti-GD-2 (disialoganglioside) antibody approved for use in post-consolidation care of patients with high-risk neuroblastoma. GD-2 receptors are also expressed in cerebellar neurons, melanocytes, and peripheral sensory nerve fibers in normal human tissue. Given this pattern of expression, pain is a common and often infusion rate-limiting adverse effect, with greater than 50% of patients experiencing severe (Grade 3 or above) pain. Standard pain management for Dinutuximab infusions at our center includes initiation of continuous infusion of opioid patient-controlled analgesia along with demand, loading, and boluses doses. Little to no data exist in the literature to describe opioid use in pediatric patients with acute, episodic pain. Therefore, this study aims to characterize opioid use in this setting. Methods: Data were collected retrospectively from the electronic medical record under a study protocol approved by the Institutional Review Board at the University of Michigan, C.S. Mott Children9s Hospital. Patients were included in the study if they had a clinical diagnosis of metastatic or relapsed high-risk neuroblastoma, received at least one Dinutuximab cycle, and were aged 2-14 at the time of admission. Daily amount of opioids, calculated as the oral morphine equivalent daily dose (MEDD), acetaminophen, and gabapentin administered were calculated. Repeated measures ANOVA was used to evaluate within-subjects changes. Results: The average age of patients was 5.7 years [range 2-14 years]. Four of eleven (36.4%) were female and 7/11 (63.6%) were male. All patients received four days of Dinutuximab infusions for an average length of 11.8 hours (SD=2.0) per day. All patients received gabapentin prophylactic treatment and an average of 3387 mg (SD=1275.5). Average total MEDD across all patients was 184.7 mg (SD=137.6) during the inpatient hospitalization. Females (p=0.003) and older patients (p=0.04) had significantly increased daily MEDD as compared to their day 1 intake. All patients experienced a fever spike and received acetaminophen (2915 mg, SD=1737.8) Older patients received higher doses of acetaminophen (p=0.007) Only 1 patient met definition of a chronic opioid user and was discharged with an outpatient opioid prescription. The remaining opioid-naive patients were discontinued on opioid treatment at the time of discharge. Conclusions: Pediatric patients on Dinutuximab therapy received a high MEDD parenteral opioids dose alongside adjunctive analgesics. Future studies are needed to determine opioid requirement trends across gender, age, and cycles in a larger cohort of patients, as well as to determine the risk of chronic opioid use in this patient population. Citation Format: Jola Mehmeti, Jae Eun Choi, Ian Wolfe, Juan Cata, Rajen Mody. Characterization of inpatient opioid use among pediatric neuroblastoma patients during Dinutuximab therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2045.

  • irinotecan temozolomide and Dinutuximab with gm csf in children with refractory or relapsed neuroblastoma a report from the children s oncology group
    Journal of Clinical Oncology, 2020
    Co-Authors: Rajen Mody, Arlene Naranjo, Wendy B. London, Mitchell B. Diccianni, Jacquelyn A. Hank, Barry L Shulkin, Marguerite T Parisi, Sabah Servaes, Fan F Zhang, Mildred Felder
    Abstract:

    PURPOSEThe combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neur...

  • phase ii trial of irinotecan temozolomide Dinutuximab granulocyte macrophage colony stimulating factor i t din gmcsf in children with relapsed refractory neuroblastoma nbl a report from the children s oncology group cog
    Journal of Clinical Oncology, 2018
    Co-Authors: Rajen Mody, Arlene Naranjo, Wendy B. London, Paul M. Sondel, Barry L Shulkin, Marguerite T Parisi, Sabah Servaes, Mitchell B Dicciani, Emily Hibbitts, Julia Gladebender
    Abstract:

    10508Background: COG ANBL1221 was a randomized Phase II selection design trial for patients (pts) with relapsed/refractory NBL. Randomization was stopped early when I/T/DIN/GMCSF was shown be the o...

  • irinotecan temozolomide with temsirolimus or Dinutuximab in children with refractory or relapsed neuroblastoma cog anbl1221 an open label randomised phase 2 trial
    Lancet Oncology, 2017
    Co-Authors: Rajen Mody, Arlene Naranjo, Wendy B. London, Mitchell B. Diccianni, Paul M. Sondel, Collin Van Ryn, Barry L Shulkin, Marguerite T Parisi, Sabah Servaes, Julia Glade L Bender
    Abstract:

    Summary Background Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or Dinutuximab to irinotecan–temozolomide in patients with relapsed or refractory neuroblastoma. Methods For this open-label, randomised, phase 2 selection design trial of the Children's Oncology Group (COG; ANBL1221), patients had to have histological verification of neuroblastoma or ganglioneuroblastoma at diagnosis or have tumour cells in bone marrow with increased urinary catecholamine concentrations at diagnosis. Patients of any age were eligible at first designation of relapse or progression, or first designation of refractory disease, provided organ function requirements were met. Patients previously treated for refractory or relapsed disease were ineligible. Computer-based randomisation with sequence generation defined by permuted block randomisation (block size two) was used to randomly assign patients (1:1) to irinotecan and temozolomide plus either temsirolimus or Dinutuximab, stratified by disease category, previous exposure to anti-GD2 antibody therapy, and tumour MYCN amplification status. Patients in both groups received oral temozolomide (100 mg/m 2 per dose) and intravenous irinotecan (50 mg/m 2 per dose) on days 1–5 of 21-day cycles. Patients in the temsirolimus group also received intravenous temsirolimus (35 mg/m 2 per dose) on days 1 and 8, whereas those in the Dinutuximab group received intravenous Dinutuximab (17·5 mg/m 2 per day or 25 mg/m 2 per day) on days 2–5 plus granulocyte macrophage colony-stimulating factor (250 μg/m 2 per dose) subcutaneously on days 6–12. Patients were given up to a maximum of 17 cycles of treatment. The primary endpoint was the proportion of patients achieving an objective (complete or partial) response by central review after six cycles of treatment, analysed by intention to treat. Patients, families, and those administering treatment were aware of group assignment. This study is registered with ClinicalTrials.gov, number NCT01767194, and follow-up of the initial cohort is ongoing. Findings Between Feb 22, 2013, and March 23, 2015, 36 patients from 27 COG member institutions were enrolled on this groupwide study. One patient was ineligible (alanine aminotransferase concentration was above the required range). Of the remaining 35 patients, 18 were randomly assigned to irinotecan–temozolomide–temsirolimus and 17 to irinotecan–temozolomide–Dinutuximab. Median follow-up was 1·26 years (IQR 0·68–1·61) among all eligible participants. Of the 18 patients assigned to irinotecan–temozolomide–temsirolimus, one patient (6%; 95% CI 0·0–16·1) achieved a partial response. Of the 17 patients assigned to irinotecan–temozolomide–Dinutuximab, nine (53%; 95% CI 29·2–76·7) had objective responses, including four partial responses and five complete responses. The most common grade 3 or worse adverse events in the temsirolimus group were neutropenia (eight [44%] of 18 patients), anaemia (six [33%]), thrombocytopenia (five [28%]), increased alanine aminotransferase (five [28%]), and hypokalaemia (four [22%]). One of the 17 patients assigned to the Dinutuximab group refused treatment after randomisation; the most common grade 3 or worse adverse events in the remaining 16 patients evaluable for safety were pain (seven [44%] of 16), hypokalaemia (six [38%]), neutropenia (four [25%]), thrombocytopenia (four [25%]), anaemia (four [25%]), fever and infection (four [25%]), and hypoxia (four [25%]); one patient had grade 4 hypoxia related to therapy that met protocol-defined criteria for unacceptable toxicity. No deaths attributed to protocol therapy occurred. Interpretation Irinotecan–temozolomide–Dinutuximab met protocol-defined criteria for selection as the combination meriting further study whereas irinotecan–temozolomide–temsirolimus did not. Irinotecan–temozolomide–Dinutuximab shows notable anti-tumour activity in patients with relapsed or refractory neuroblastoma. Further evaluation of biomarkers in a larger cohort of patients might identify those most likely to respond to this chemoimmunotherapeutic regimen. Funding National Cancer Institute.

  • phase ii randomized trial of irinotecan temozolomide i t with temsirolimus tem or Dinutuximab plus granulocyte colony stimulating factor din gmcsf in children with refractory or relapsed neuroblastoma a report from the children s oncology group cog
    Journal of Clinical Oncology, 2016
    Co-Authors: Rajen Mody, Arlene Naranjo, Wendy B. London, Paul M. Sondel, Collin Van Ryn, Barry L Shulkin, Marguerite T Parisi, Sabah Servaes, Mitchell B Dicciani, John M Maris
    Abstract:

    10502Background: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of I/T has activity in patients with relapsed disease, and the toxicity profile of I/T makes it an excellent backbone for study of new agents. Temsirolimus (TEM) and Dinutuximab (DIN) were selected for testing in combination with I/T in subjects with relapsed, progressive or refractory neuroblastoma. Methods: COG ANBL1221, a randomized Phase II selection design trial, compared response and toxicity in subjects treated with I/T in combination with either TEM (Arm A) or DIN/GM-CSF (Arm B). Patients were eligible at first relapse/progression or first designation of primary refractory disease. Randomization was stratified based on prior therapy and MYCNstatus. Cycles were administered every 21 days. Partial and complete responses (PR, CR) were confirmed centrally. Results: Thirty-five eligible patients were enrolled. Median age was 5.7 years (range 2.1-16.2), 24 pts had measurable disease (12 per arm)...

Martin J Edelman - One of the best experts on this subject based on the ideXlab platform.