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A Study of Therapeutic Iobenguane (131-I) for Relapsed, High-Risk Neuroblastoma Subjects (OPTIMUM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03561259
Recruitment Status : Recruiting
First Posted : June 19, 2018
Last Update Posted : January 22, 2020
Information provided by (Responsible Party):
Jubilant DraxImage Inc.

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in patients with neuroblastoma, who relapsed.

Condition or disease Intervention/treatment Phase
Neuroblastoma Neuroectodermal Tumors Neoplasms Drug: 131I-MIBG Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

OPTIMUM (MIBG 2014-01) is a Phase II, single-arm, non-randomized, open-label study of therapeutic 131I-iobenguane (131I-MIBG) for the treatment of neuroblastoma. The study will be conducted in male and female subjects, greater than 1 year of age, with iobenguane avid, relapsed, high-risk neuroblastoma.

Subjects will receive 18 mCi/kg of 131I-MIBG intravenously, and if the subject qualifies, the subject will receive the second 18 mCi/kg 131I-MIBG treatment (no sooner than 6 weeks following the first therapeutic 131I-MIBG treatment). Subject must have an overall response of stable disease or better, as assessed by the Investigator, and meet certain predefined criteria to receive the second treatment.

Following a screening period of up to 4 weeks, the duration in the study treatment phase for an individual subject, who receives two treatments, is up to 22 weeks. For an individual subject, who receives one treatment only, the duration of the treatment phase is 16 weeks. In addition, there is a 2-year follow-up after the treatment phase, during which assessments will be performed to assess disease progression, as well as record adverse events.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm, non-randomized, open-label study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Single-arm Study of Therapeutic Iobenguane (131-I) for Relapsed, High-risk Neuroblastoma Subjects
Actual Study Start Date : October 21, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
Experimental: 131I-MIBG
Drug: 131I-MIBG
Subjects will receive 18 mCi/kg of 131I-MIBG administered via either a central or a peripheral intravenous catheter over 1.5 to 2 hours on Day 0. The maximum absolute dose of 131I-MIBG on this protocol is determined by institution therapeutic limits and will not exceed 1,000 mCi. Subjects with an overall response of stable disease or better as assessed by the Investigator, and who meet certain predefined criteria, may receive a second 18 mCi/kg 131I-MIBG treatment no sooner than 6 weeks following the first therapeutic 131I-MIBG treatment.
Other Names:
  • I-131 meta-iodobenzylguanidine
  • Iobenguane I-131 MIBG Injection

Primary Outcome Measures :
  1. Overall Response [ Time Frame: 6 weeks after the last 131I-MIBG treatment and a confirmatory assessment at least 6 weeks thereafter (at least 12 weeks from the end of treatment) ]
    Overall response (Yes/No) is based on the International Neuroblastoma Response Crtieria (INRC, published 2017). The INRC will be calculated based on 123I-iobenguane scans, CT/MRI, and bone marrow biopsies and aspirates. A "Yes" is defined as complete response, partial response or minor response. A "No" response is defined as stable disease or progressive disease.

Secondary Outcome Measures :
  1. Overall Response at 6 weeks after 131I-MIBG treatment [ Time Frame: 6 weeks after the last 131I-MIBG treatment (first or second treatment). ]
  2. Durability of Effect of Overall Response (Yes/No) [ Time Frame: For all tumour assessment data collected throughout the study (up to the end of the 2-year follow-up). ]
  3. Relative Curie Extension Score [ Time Frame: 6 weeks after the last 131I-MIBG treatment. ]
  4. Durability of Effect of Relative Curie Extension Score [ Time Frame: For all tumour assessment data collected throughout the study (up to the end of the 2-year follow-up). ]

Other Outcome Measures:
  1. Incidence of Adverse Events (CTCAE Version 5.0) [ Time Frame: Up to 22 weeks ]
  2. Incidence of Serious Adverse Events [ Time Frame: Through study completion, up to 2.5 years. ]
  3. Whole Body Radiation Dose [ Time Frame: After each 131I-MIBG treatment for up to 120 hours. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Subjects with a diagnosis of iobenguane avid, relapsed, high-risk neuroblastoma based on revised INRC criteria who have completed at least one cycle of induction and consolidation therapy with an INRC criterion of partial response or better, and then showed new progressive disease (revised INRC criteria progressive disease) as described in Park, et al. (2017).This may include one or more of the following drugs: cyclophosphamide or ifosfamide, cisplatin or carboplatin, vincristine, doxorubicin (adriamycin), etoposide, topotecan, and/or busulfan and melphalan (sometimes used during stem cell transplant) and/or immunotherapy. (If a subject is symptomatic and for logistical reasons cannot be treated immediately with 131I-MIBG, 1 to 2 cycles of "bridging chemotherapy" or immunotherapy will be permitted. If "bridging chemotherapy" or immunotherapy is applied, approximately 4 weeks will be required for reassessment of the baseline including tumor assessment.
  2. Must be therapeutic 131I-MIBG naive.
  3. All soft tissue lesions identified on CT/MRI scans must be iobenguane-avid lesions on an iobenguane (123I) scan or any non iobenguane avid lesions biopsy proven to be non-tumor lesions.
  4. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least 2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment).
  5. If a man, must agree to use an adequate contraception method as deemed appropriate by the Investigator (e.g., vasectomy, condoms) or partner using effective contraception and to not donate sperm during the study and for 90 days after receiving the last dose of study drug.
  6. If a woman of childbearing potential, have a negative serum pregnancy test result prior to each dosing and, if sexually active, be practicing an effective method of birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout the study.
  7. Age at study entry ≥1 year.
  8. Previous platelet transfusions are permitted, as long as the subject has a platelet count ≥50,000/μL without transfusion support for at least 1 week.
  9. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
  10. An absolute neutrophil count ≥750/μL without growth factor for 5 days.
  11. Liver function parameter results: total bilirubin ≤1.5 × upper limit of normal for age, and serum glutamic-pyruvic transaminase (alanine aminotransferase) [SGPT (ALT)] and serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) [SGOT (AST)] <3 × upper limit of normal (note that for ALT, the upper limit of normal for all sites is defined as 45 U/L).
  12. Normal thyroid function as measured by T4 and TSH or have abnormal results that are not considered clinically important by the Investigator or may be receiving levothyroxine.
  13. Cardiac Function: Ejection fraction (≥55%) documented by echocardiogram within 1 month prior to Visit 1 (baseline).
  14. Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance Status Performance Status (for subjects 1 to 16 years of age) ≥50%.
  15. Full recovery from the toxic effects of any prior therapy.

Exclusion Criteria:

  1. Evidence of non-avid iobenguane lesions on iobenguane (123I) scan including soft tissue disease on CT/MRI that is not iobenguane-avid.
  2. Subjects with primary refractory disease.
  3. Subjects within 5 half-lives after any antibody-based immunotherapy, or have not recovered from effects of any biologic therapy.
  4. Subjects that are refractory to the prior treatment regimen.
  5. Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
  6. Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit 1 are excluded. Those who have received allogeneic stem cell treatment more than 4 months from Visit 1 must have recovered and have no active graft versus host disease (GVHD) to be eligible.
  7. History of local radiation therapy within the last 3 months.
  8. History of total body irradiation.
  9. Subjects do not have adequate renal function defined as adjusted serum creatinine ≥1.5 × upper limit of normal for sex and age.
  10. Subjects who are on hemodialysis.
  11. Pregnancy or breastfeeding.
  12. Significant active infections including active hepatitis B, or hepatitis C infection, or known infection with human immunodeficiency virus (HIV) (testing for HIV is not required prior to study entry).
  13. Clinically important cardiac, pulmonary, and hepatic impairment.

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 identifier (NCT number): NCT03561259

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Contact: Norman LaFrance, MD,FACP 267-475-2192

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United States, California
UCSF Pediatric Hematology/Oncology Recruiting
San Francisco, California, United States, 94158
Contact: Debbie Lara    415-476-2218   
Principal Investigator: Kieuhoa Vo, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Astrid Eder    720-777-8531   
Principal Investigator: Margaret Macy, MD         
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Melissa Z Marx, MPH    773-702-2927   
Principal Investigator: Ami V Desai, MD         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Roxane Mitten    319-356-1212   
Principal Investigator: Mariko Sato, MD, PhD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Catherine M Clinton, MS    617-632-5556   
Principal Investigator: Suzanne Shusterman, MD         
United States, North Carolina
Carolinas Medical Center/Levine Children's Hospital (Atrium Health) Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Katherine Farmer    704-641-7350   
Principal Investigator: Javier E Osterheld, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Lori Backus    513-636-2047   
Principal Investigator: Brian Weiss, MD         
United States, Texas
University of Texas Southwestern Medical Center, Children's Health Recruiting
Dallas, Texas, United States, 75235
Contact: Beverly Kleiber, PhD, CCRP    214-456-1003   
Principal Investigator: Tanya Watt, MD         
Cook Children's Hematology/Oncology Center Recruiting
Fort Worth, Texas, United States, 76104
Contact: Juli Ramirez    682-885-2580   
Principal Investigator: Meaghan Granger, MD         
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Rosalynn Santos    832-824-4167   
Principal Investigator: Jennifer Foster, MD         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Christine Goetz, BA,CCRC    206-884-1149   
Principal Investigator: Navin R Pinto, MD         
Sponsors and Collaborators
Jubilant DraxImage Inc.
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Study Director: Norman LaFrance, MD,FACP Jubilant DraxImage Inc.
Study Director: Alexandre Brkovic, PhD Jubilant DraxImage Inc.
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Responsible Party: Jubilant DraxImage Inc. Identifier: NCT03561259    
Other Study ID Numbers: MIBG 2014-01
First Posted: June 19, 2018    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jubilant DraxImage Inc.:
Iobenguane Avid High-risk Neuroblastoma
Additional relevant MeSH terms:
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Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action