Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors: A report of the Children's Oncology Group

Michael J. Burke, Charlotte Ahern, Brenda J. Weigel, John T. Poirier, Charles M. Rudin, Yingbei Chen, Timothy P. Cripe, M. Brooke Bernhardt, Susan M. Blaney

Research output: Contribution to journalArticle

Abstract

Background: To determine the MTD of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors. Patients (≥3-≤21 years) with neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features were eligible. Procedure: Part A (single dose of NTX-010) enrolled 13 patients at three dose levels (1×109 viral particles (vp)/kg [n=6], 1×1010vp/kg [n=3], 1×1011vp/kg [n=4]). Diagnoses included neuroblastoma (n=9), rhabdomyosarcoma (n=2), carcinoid tumor (n=1), and adrenocorticocarcinoma (n=1). Part B added cyclophosphamide (CTX) (oral CTX (25mg/m2/day) days 1-14 and IV CTX (750mg/m2) days 8 and 29) to two doses of NTX-010 (1×1011vp/kg, days 8 and 29). Nine patients enrolled to Part B. Diagnoses included neuroblastoma (n=3), rhabdomyosarcoma (n=1), Wilms tumor (n=3), and adrenocorticocarcinoma (n=2). Results: Twelve patients on Part A were evaluable for toxicity. There was a single DLT (grade 3 pain) at dose level 1. Additional grade ≥3 related adverse events (AEs) included leukopenia (n=1), neutropenia (n=3), lymphopenia (n=3), and tumor pain (n=1). No DLTs occurred on part B. Other grade ≥3 related AEs on Part B included: Leukopenia (n=3), nausea (n=1), emesis (n=1), anemia (n=1), neutropenia (n=4), platelets (n=1), alanine aminotransferase (n=1), and lymphopenia (n=2). All patients cleared NTX-010 from blood and stool by 3 weeks with 17/18 patients developing neutralizing antibodies. Conclusion: NTX-010 is feasible and tolerable at the dose levels tested in pediatric patients with relapsed/refractory solid tumors either alone or in combination with cyclophosphamide. However, despite the addition of cyclophosphamide, neutralizing antibodies appeared to limit applicability. Pediatr Blood Cancer 2015;62:743-750.

Original languageEnglish (US)
Pages (from-to)743-750
Number of pages8
JournalPediatric Blood and Cancer
Volume62
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

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Viruses
Neuroblastoma
Neoplasms
Cyclophosphamide
Lymphopenia
Rhabdomyosarcoma
Leukopenia
Neutralizing Antibodies
Neutropenia
Pain
Neuroendocrine Tumors
Carcinoid Tumor
Alanine Transaminase
Virion
Nausea
Vomiting
Anemia
Blood Platelets
Pediatrics

Keywords

  • Oncolytic
  • Pediatric
  • Relapsed
  • Seneca valley virus
  • Solid tumors

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors : A report of the Children's Oncology Group. / Burke, Michael J.; Ahern, Charlotte; Weigel, Brenda J.; Poirier, John T.; Rudin, Charles M.; Chen, Yingbei; Cripe, Timothy P.; Bernhardt, M. Brooke; Blaney, Susan M.

In: Pediatric Blood and Cancer, Vol. 62, No. 5, 01.05.2015, p. 743-750.

Research output: Contribution to journalArticle

Burke, MJ, Ahern, C, Weigel, BJ, Poirier, JT, Rudin, CM, Chen, Y, Cripe, TP, Bernhardt, MB & Blaney, SM 2015, 'Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors: A report of the Children's Oncology Group', Pediatric Blood and Cancer, vol. 62, no. 5, pp. 743-750. https://doi.org/10.1002/pbc.25269
Burke, Michael J. ; Ahern, Charlotte ; Weigel, Brenda J. ; Poirier, John T. ; Rudin, Charles M. ; Chen, Yingbei ; Cripe, Timothy P. ; Bernhardt, M. Brooke ; Blaney, Susan M. / Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors : A report of the Children's Oncology Group. In: Pediatric Blood and Cancer. 2015 ; Vol. 62, No. 5. pp. 743-750.
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abstract = "Background: To determine the MTD of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors. Patients (≥3-≤21 years) with neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features were eligible. Procedure: Part A (single dose of NTX-010) enrolled 13 patients at three dose levels (1×109 viral particles (vp)/kg [n=6], 1×1010vp/kg [n=3], 1×1011vp/kg [n=4]). Diagnoses included neuroblastoma (n=9), rhabdomyosarcoma (n=2), carcinoid tumor (n=1), and adrenocorticocarcinoma (n=1). Part B added cyclophosphamide (CTX) (oral CTX (25mg/m2/day) days 1-14 and IV CTX (750mg/m2) days 8 and 29) to two doses of NTX-010 (1×1011vp/kg, days 8 and 29). Nine patients enrolled to Part B. Diagnoses included neuroblastoma (n=3), rhabdomyosarcoma (n=1), Wilms tumor (n=3), and adrenocorticocarcinoma (n=2). Results: Twelve patients on Part A were evaluable for toxicity. There was a single DLT (grade 3 pain) at dose level 1. Additional grade ≥3 related adverse events (AEs) included leukopenia (n=1), neutropenia (n=3), lymphopenia (n=3), and tumor pain (n=1). No DLTs occurred on part B. Other grade ≥3 related AEs on Part B included: Leukopenia (n=3), nausea (n=1), emesis (n=1), anemia (n=1), neutropenia (n=4), platelets (n=1), alanine aminotransferase (n=1), and lymphopenia (n=2). All patients cleared NTX-010 from blood and stool by 3 weeks with 17/18 patients developing neutralizing antibodies. Conclusion: NTX-010 is feasible and tolerable at the dose levels tested in pediatric patients with relapsed/refractory solid tumors either alone or in combination with cyclophosphamide. However, despite the addition of cyclophosphamide, neutralizing antibodies appeared to limit applicability. Pediatr Blood Cancer 2015;62:743-750.",
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T1 - Phase I trial of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors

T2 - A report of the Children's Oncology Group

AU - Burke, Michael J.

AU - Ahern, Charlotte

AU - Weigel, Brenda J.

AU - Poirier, John T.

AU - Rudin, Charles M.

AU - Chen, Yingbei

AU - Cripe, Timothy P.

AU - Bernhardt, M. Brooke

AU - Blaney, Susan M.

PY - 2015/5/1

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N2 - Background: To determine the MTD of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors. Patients (≥3-≤21 years) with neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features were eligible. Procedure: Part A (single dose of NTX-010) enrolled 13 patients at three dose levels (1×109 viral particles (vp)/kg [n=6], 1×1010vp/kg [n=3], 1×1011vp/kg [n=4]). Diagnoses included neuroblastoma (n=9), rhabdomyosarcoma (n=2), carcinoid tumor (n=1), and adrenocorticocarcinoma (n=1). Part B added cyclophosphamide (CTX) (oral CTX (25mg/m2/day) days 1-14 and IV CTX (750mg/m2) days 8 and 29) to two doses of NTX-010 (1×1011vp/kg, days 8 and 29). Nine patients enrolled to Part B. Diagnoses included neuroblastoma (n=3), rhabdomyosarcoma (n=1), Wilms tumor (n=3), and adrenocorticocarcinoma (n=2). Results: Twelve patients on Part A were evaluable for toxicity. There was a single DLT (grade 3 pain) at dose level 1. Additional grade ≥3 related adverse events (AEs) included leukopenia (n=1), neutropenia (n=3), lymphopenia (n=3), and tumor pain (n=1). No DLTs occurred on part B. Other grade ≥3 related AEs on Part B included: Leukopenia (n=3), nausea (n=1), emesis (n=1), anemia (n=1), neutropenia (n=4), platelets (n=1), alanine aminotransferase (n=1), and lymphopenia (n=2). All patients cleared NTX-010 from blood and stool by 3 weeks with 17/18 patients developing neutralizing antibodies. Conclusion: NTX-010 is feasible and tolerable at the dose levels tested in pediatric patients with relapsed/refractory solid tumors either alone or in combination with cyclophosphamide. However, despite the addition of cyclophosphamide, neutralizing antibodies appeared to limit applicability. Pediatr Blood Cancer 2015;62:743-750.

AB - Background: To determine the MTD of Seneca Valley Virus (NTX-010) in children with relapsed/refractory solid tumors. Patients (≥3-≤21 years) with neuroblastoma, rhabdomyosarcoma, or rare tumors with neuroendocrine features were eligible. Procedure: Part A (single dose of NTX-010) enrolled 13 patients at three dose levels (1×109 viral particles (vp)/kg [n=6], 1×1010vp/kg [n=3], 1×1011vp/kg [n=4]). Diagnoses included neuroblastoma (n=9), rhabdomyosarcoma (n=2), carcinoid tumor (n=1), and adrenocorticocarcinoma (n=1). Part B added cyclophosphamide (CTX) (oral CTX (25mg/m2/day) days 1-14 and IV CTX (750mg/m2) days 8 and 29) to two doses of NTX-010 (1×1011vp/kg, days 8 and 29). Nine patients enrolled to Part B. Diagnoses included neuroblastoma (n=3), rhabdomyosarcoma (n=1), Wilms tumor (n=3), and adrenocorticocarcinoma (n=2). Results: Twelve patients on Part A were evaluable for toxicity. There was a single DLT (grade 3 pain) at dose level 1. Additional grade ≥3 related adverse events (AEs) included leukopenia (n=1), neutropenia (n=3), lymphopenia (n=3), and tumor pain (n=1). No DLTs occurred on part B. Other grade ≥3 related AEs on Part B included: Leukopenia (n=3), nausea (n=1), emesis (n=1), anemia (n=1), neutropenia (n=4), platelets (n=1), alanine aminotransferase (n=1), and lymphopenia (n=2). All patients cleared NTX-010 from blood and stool by 3 weeks with 17/18 patients developing neutralizing antibodies. Conclusion: NTX-010 is feasible and tolerable at the dose levels tested in pediatric patients with relapsed/refractory solid tumors either alone or in combination with cyclophosphamide. However, despite the addition of cyclophosphamide, neutralizing antibodies appeared to limit applicability. Pediatr Blood Cancer 2015;62:743-750.

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KW - Seneca valley virus

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