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MIBG With Dinutuximab

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ClinicalTrials.gov Identifier: NCT03332667
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : September 10, 2018
Sponsor:
Collaborator:
United Therapeutics
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium

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 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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Radiation: 131I-MIBG Drug: Ch14.18 Monoclonal Antibody Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of 131I-MIBG With Dinutuximab for Relapsed/Refractory Neuroblastoma
Actual Study Start Date : September 5, 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma
Drug Information available for: Dinutuximab

Arm Intervention/treatment
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
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




Primary Outcome Measures :
  1. 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.

  2. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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



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Ages Eligible for Study:   1 Year to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03332667


Contacts
Contact: Araz Marachelian, MD, MS 323-361-5687 amarachelian@chla.usc.edu

Locations
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027-0700
Contact: Araz Marachelian, MD    323-361-5687    amarachelian@chla.usc.edu   
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143
Contact: Katherine K. Matthay, MD    415-476-3831    matthayK@peds.ucsf.edu   
United States, Colorado
Children Hospital of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Margaret Macy, MD    720-777-8856    Margaret.macy@childrenscolorado.org   
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus Recruiting
Atlanta, Georgia, United States, 30322
Contact: Kelly Goldsmith, MD    404-785-0853    kgoldsm@emory.edu   
United States, Illinois
University of Chicago, Comer Children's Hospital Recruiting
Chicago, Illinois, United States, 60637
Contact: Ami L. Desai, MD    773-843-3943    adesai12@peds.bsd.uchicago.edu   
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Suzanne Shusterman, MD    617-632-4901    suzanne_shusterman@dfci.harvard.edu   
United States, Michigan
C.S Mott Children's Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Rajen Mody, MD       rmody@umich.edu   
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Patrick Thompson, MD       patom@email.unc.edu   
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Brian Weiss, MD    513-636-9863    brian.weiss@chmcc.org   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104-4318
Contact: Yael Mosse, MD    215-590-0965    mosse@chop.edu   
United States, Texas
Cook Children's Healthcare System Recruiting
Fort Worth, Texas, United States, 76104
Contact: Meaghan Granger, MD    682-885-4007      
United States, Washington
Children's Hospital and Regional Medical Center - Seattle Recruiting
Seattle, Washington, United States, 98105
Contact: Navin Pinto, MD    206-987-5783    navin.pinto@seattlechildrens.org   
Sponsors and Collaborators
New Approaches to Neuroblastoma Therapy Consortium
United Therapeutics
Investigators
Study Chair: Thomas Cash, MD Children's Healthcare of Atlanta
Study Director: Araz Marachelian, MD, MS Children's Hospital Los Angeles

Responsible Party: New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier: NCT03332667     History of Changes
Other Study ID Numbers: NANT2017-01
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antibodies
Immunoglobulins
Antibodies, Monoclonal
3-Iodobenzylguanidine
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Radiopharmaceuticals