Clinical Trials /

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

NCT03561259

Description:

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

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Therapeutic Iobenguane (131-I) for Relapsed, High-Risk Neuroblastoma Subjects
  • Official Title: A Phase II Single-arm Study of Therapeutic Iobenguane (131-I) for Relapsed, High-risk Neuroblastoma Subjects

Clinical Trial IDs

  • ORG STUDY ID: MIBG 2014-01
  • NCT ID: NCT03561259

Conditions

  • Neuroblastoma
  • Neuroectodermal Tumors
  • Neoplasms

Interventions

DrugSynonymsArms
131I-MIBGI-131 meta-iodobenzylguanidine, Iobenguane I-131 MIBG Injection131I-MIBG

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
131I-MIBGExperimental131I-MIBG
  • 131I-MIBG

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description: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

Measure:Overall Response at 6 weeks after 131I-MIBG treatment
Time Frame:6 weeks after the last 131I-MIBG treatment (first or second treatment).
Safety Issue:
Description:
Measure: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).
Safety Issue:
Description:
Measure:Relative Curie Extension Score
Time Frame:6 weeks after the last 131I-MIBG treatment.
Safety Issue:
Description:
Measure: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).
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jubilant DraxImage Inc.

Trial Keywords

  • Iobenguane Avid High-risk Neuroblastoma
  • 3-Iodobenzylguanidine
  • Radiopharmaceutical

Last Updated

January 20, 2020