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Trial record 1 of 2 for:    Phase 1 study of 131I-MIBG with Dinutuximab for Relapsed or Refractory Neuroblastoma
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MIBG With Dinutuximab +/- Vorinostat

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ClinicalTrials.gov Identifier: NCT03332667
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : January 20, 2021
Sponsor:
Collaborator:
United Therapeutics
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium

Tracking Information
First Submitted Date  ICMJE November 2, 2017
First Posted Date  ICMJE November 6, 2017
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE September 5, 2018
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2021)
  • Determination of maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of 131I-MIBG with Dinutuximab [ Time Frame: Approximately 2 years ]
    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.
  • Determination of maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of vorinostat in combination with 131I-MIBG and Dinutuximab [ Time Frame: Approximately 2 years ]
    By dose level.Two to six evaluable patients will be entered at the proposed dose level for determination of the maximum tolerated dose.
  • To define and describe the toxicities of 131I-MIBG in combination with dinutuximab administered on this schedule to this population. [ Time Frame: 6 months ]
    Toxicity will be graded using the CTCAE criteria, version 4. The CTCAE provides descriptive terminology and a grading scale for each adverse event listed. A copy of the CTCAE can be downloaded from the CTEP home page (http://ctep.cancer.gov).
  • To define and describe the toxicities of vorinostat in combination with 131I-MIBG and dinutuximab administered on this schedule to this population. [ Time Frame: 6 months ]
    Toxicity will be graded using the CTCAE criteria, version 4. The CTCAE provides descriptive terminology and a grading scale for each adverse event listed. A copy of the CTCAE can be downloaded from the CTEP home page (http://ctep.cancer.gov).
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
  • Determination of maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of 131I-MIBG with Dinutuximab [ Time Frame: Approximately 2 years ]
    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.
  • To define and describe the toxicities of 131I-MIBG in combination with dinutuximab administered on this schedule to this population. [ Time Frame: 6 months ]
    Toxicity will be graded using the CTCAE criteria, version 4. The CTCAE provides descriptive terminology and a grading scale for each adverse event listed. A copy of the CTCAE can be downloaded from the CTEP home page (http://ctep.cancer.gov).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
  • 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.] ]
    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.
  • 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 ]
    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.
  • 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 ]
    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.
  • 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 ]
    Bone marrow response is assessed by morphologic and immunohistologic evaluation of bilateral bone marrow aspirates and biopsies
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MIBG With Dinutuximab +/- Vorinostat
Official Title  ICMJE A Phase I Study of 131I-MIBG With Dinutuximab +/- Vorinostat for Relapsed/Refractory Neuroblastoma
Brief Summary 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 rolling 6 dose escalation design to determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6 patients will then be enrolled. If tolerable, vorinostat will then be added to the third dose level. A 6 patient expansion cohort 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 and vorinostat aims to determine the recommended phase 2 pediatric dose of these three therapies in combination.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroblastoma
Intervention  ICMJE
  • Radiation: 131I-MIBG
    Patients will receive 131I-MIBG on day 1. 131I-MIBG dose will be based on the dose level assigned at the time of patient registration
    Other Names:
    • 131I-Metaiodobenzylguanidine
    • Iobenguane sulfate
    • m-Iodobenzylguanidine sulfate
    • MIBG
  • Drug: Ch14.18 Monoclonal Antibody
    Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab dose will be based on the dose level assigned at the time of patient registration.
    Other Names:
    • Chimeric Monoclonal Antibody 14.18
    • MAB Ch 14.18
    • Unituxin
    • Ch14.18
    • Dinutuximab
  • Drug: Vorinostat
    Vorinostat will be given on day 0-13. Vorinostat dose will be based on the dose level assigned at the time of patient registration.
    Other Name: Zolina
Study Arms  ICMJE
  • Experimental: 131I-MIBG with Dinutuximab
    Patients 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
    Interventions:
    • Radiation: 131I-MIBG
    • Drug: Ch14.18 Monoclonal Antibody
  • Experimental: 131I-MIBG with Dinutuximab and Vorinostat
    Patients will receive vorinostat on days 0-13. 131I-MIBG will be received 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
    Interventions:
    • Radiation: 131I-MIBG
    • Drug: Ch14.18 Monoclonal Antibody
    • Drug: Vorinostat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 15, 2021)
32
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2017)
24
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Araz Marachelian, MD, MS 323-361-5687 amarachelian@chla.usc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03332667
Other Study ID Numbers  ICMJE NANT2017-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party New Approaches to Neuroblastoma Therapy Consortium
Study Sponsor  ICMJE New Approaches to Neuroblastoma Therapy Consortium
Collaborators  ICMJE United Therapeutics
Investigators  ICMJE
Study Chair: Thomas Cash, MD Children's Healthcare of Atlanta
Study Director: Araz Marachelian, MD, MS Children's Hospital Los Angeles
PRS Account New Approaches to Neuroblastoma Therapy Consortium
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP