Clinical Trials /

MIBG With Dinutuximab

NCT03332667

Description:

131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial, 131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal antibody. This study will utilize a traditional Phase I dose escalation 3+3 design to determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6 patients may then be enrolled.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MIBG With Dinutuximab
  • Official Title: A Phase I Study of 131I-MIBG With Dinutuximab for Relapsed/Refractory Neuroblastoma

Clinical Trial IDs

  • ORG STUDY ID: NANT2017-01
  • NCT ID: NCT03332667

Conditions

  • Neuroblastoma

Interventions

DrugSynonymsArms
Ch14.18 Monoclonal AntibodyChimeric Monoclonal Antibody 14.18, MAB Ch 14.18, Unituxin, Ch14.18, Dinutuximab131I-MIBG with Dinutuximab

Purpose

131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial, 131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal antibody. This study will utilize a traditional Phase I dose escalation 3+3 design to determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6 patients may then be enrolled.

Detailed Description

      131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for
      neuroblastoma patients with refractory or relapsed disease. Data from pre-clinical and adult
      studies suggest that radiation can enhance the efficacy of immunotherapy and targeted
      therapies such as dinutuximab. This first pediatric phase 1 trial of 131I-MIBG in combination
      with dinutuximab aims to determine the recommended phase 2 pediatric dose of these two
      therapies in combination.
    

Trial Arms

NameTypeDescriptionInterventions
131I-MIBG with DinutuximabExperimentalPatients will receive 131I-MIBG on day 1. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab and 131I-MIBG dose will be based on the dose level assigned at the time of patient registration. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy
  • Ch14.18 Monoclonal Antibody

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a diagnosis of neuroblastoma either by histologic verification of
             neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased
             urinary catecholamines

          -  Patients must have high risk neuroblastoma according to COG risk classification at the
             time of study registration. Patients who were initially considered low or intermediate
             risk, but then reclassified as high risk are also eligible.

          -  Patients must have at least ONE of the following: 1) Recurrent/progressive disease at
             any time prior to study enrollment, 2) Refractory disease, 3) Persistent disease

          -  Patients must have at least ONE of the following: 1) Bone disease, 2) Any amount of
             neuroblastoma tumor cells in the bone marrow, 3) At least one soft tissue lesion that
             meets criteria for a TARGET lesion, 4) At least one non-target soft tissue lesion that
             is not measurable, but had a biopsy positive for neuroblastoma and/or
             ganglioneuroblastoma at any time prior to enrollment or is MIBG avid

          -  Patients must have a Lansky (≤16 years) or Karnofsky (> 16 years) score of at least 50

          -  Patients must have fully recovered from the acute toxic effects of all prior
             chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

          -  Patients must not have received any of the specified therapies as stated in the
             protocol in the time period prior to registration

          -  Patients must not be receiving any other anti-cancer agents or radiotherapy at the
             time of study entry or while on study.

          -  Patients must not be receiving other investigational medications (covered under
             another IND) within 30 days of study entry or while on study.

          -  Patients must not be receiving chronic systemic corticosteroids at doses greater than
             physiologic dosing (inhaled corticosteroids acceptable).

          -  Patient must meet the organ function and system function requirements as stated in the
             protocol

        Exclusion Criteria:

          -  Pregnancy, breast feeding, or unwillingness to use effective contraception during the
             study.

          -  Patients who, in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study.

          -  Patients with disease of any major organ system that would compromise their ability to
             withstand therapy.

          -  Patients who have received prior allogeneic stem cell transplant

          -  Patients who are on hemodialysis.

          -  Patients with an active or uncontrolled infection.

          -  Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
             hepatitis C.

          -  Patients and/or families who are physically and psychologically unable to cooperate
             with the radiation safety isolation.

          -  Patients with a history of having to discontinue anti-GD2 antibody therapy due to
             toxicity are not eligible.

          -  Prior anti-GD2 therapy is not otherwise an exclusionary criteria unless it was given
             in combination with therapeutic 131I-MIBG.

          -  Patient declines participation in NANT 2004-05, the NANT Biology Study
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of 131I-MIBG with Dinutuximab
Time Frame:Approximately 2 years
Safety Issue:
Description:By dose level.Two to six evaluable patients will be entered at each of the three dose levels for determination of the maximum tolerated dose.

Secondary Outcome Measures

Measure:Evaluation of overall response
Time Frame:Overall response is assessed at 8, 16, 24, 40, and 56 weeks from start of therapy, and then every 16 weeks, and at end of protocol therapy; an average of 24 weeks.]
Safety Issue:
Description:Overall response is the measure that will be used to assess anti-tumor activity, and is determined by integration of the soft tissue response, bone response, and bone marrow response according to the NANT Response Criteria, Version 2.0 definitions. Responders are defined as patients with an overall response of Complete Response, Complete Response-Minimal Disease, or Partial Response.
Measure:Evaluation of soft tissue response
Time Frame:Soft tissue response is assessed at 8, 16, 24, 40, and 56 weeks from start of therapy, and then every 16 weeks, and at end of protocol therapy; an average of 24 weeks
Safety Issue:
Description:Soft tissue response is assessed by CT/MRI scans using RECIST criteria to define measurable lesions with the addition of MIBG and/or FDG-PET (only for MIBG non-avid tumors) avidity and/or biopsy to define target lesions for response.
Measure:Evaluation of bone response
Time Frame:Bone response is assessed at 8, 16, 24, 40, and 56 weeks from start of therapy, and then every 16 weeks, and at end of protocol therapy; an average of 24 weeks
Safety Issue:
Description:Bone response is assessed by MIBG scans for MIBG avid tumors, and by FDG-PET scans for MIBG non-avid tumors, using sectors 1-9 of the Curie scoring to determine the relative score at each response timepoint.
Measure:Evaluation of bone marrow response
Time Frame:Bone marrow response is assessed at 8, 16, 24, 40, and 56 weeks from start of therapy, and then every 16 weeks, and at end of protocol therapy; an average of 24 weeks
Safety Issue:
Description:Bone marrow response is assessed by morphologic and immunohistologic evaluation of bilateral bone marrow aspirates and biopsies

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:New Approaches to Neuroblastoma Therapy Consortium

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