MIBG With Dinutuximab +/- Vorinostat
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| ClinicalTrials.gov Identifier: NCT03332667 |
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Recruitment Status :
Recruiting
First Posted : November 6, 2017
Last Update Posted : January 20, 2021
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Sponsor:
New Approaches to Neuroblastoma Therapy Consortium
Collaborator:
United Therapeutics
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neuroblastoma | Radiation: 131I-MIBG Drug: Ch14.18 Monoclonal Antibody Drug: Vorinostat | Phase 1 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 32 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I Study of 131I-MIBG With Dinutuximab +/- Vorinostat 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 Genetics related topics:
Neuroblastoma
MedlinePlus related topics:
Neuroblastoma
| Arm | Intervention/treatment |
|---|---|
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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
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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:
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:
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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
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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:
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:
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 |
Primary Outcome Measures :
- 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).
Secondary Outcome Measures :
- 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
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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: Kieuhoa Vo, MD | |
| 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 |
| Other Study ID Numbers: |
NANT2017-01 |
| First Posted: | November 6, 2017 Key Record Dates |
| Last Update Posted: | January 20, 2021 |
| Last Verified: | January 2021 |
| 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:
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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 Antineoplastic Agents, Immunological Vorinostat |
3-Iodobenzylguanidine Ch14.18 monoclonal antibody Antibodies Immunoglobulins Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Histone Deacetylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Radiopharmaceuticals |