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ANBL1531 A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Crizotinib Added to Intensive Therapy for Children with Newly Diagnosed High-Risk Neuroblastoma (NBL) (IND# 134379). A COG Group wide Phase 3 Study

Details

Status

closed

Study Type

Interventional

Study Phase

III

Location(s)

The Johns Hopkins Hospital

1800 Orleans St Baltimore, MD 21287

Contact Us

(410) 955-8964

Brief Summary

In this study, researchers want to find out if we can improve the treatment for subjects with high-risk NBL by adding the experimental drug 131I-MIBG or the experimental drug Crizotinib to COG recommended therapy. We also want to find out if we can reduce the number of stem cell transplants from two to one if we give the experimental drug 131I-MIBG during Induction, and use different drugs as part of the transplant chemotherapy given prior to stem cell infusion during Consolidation.

131I-MIBG is an experimental anticancer drug that has not been approved by the Food and Drug Administration (FDA) for use in treating high-risk NBL. 131I-MIBG has been used to treat NBL that did not respond to first line therapy or NBL that has come back. 131I-MIBG has been shown to be well tolerated in children with cancer. 131I-MIBG can only be given at certain hospitals and you may need to travel to another hospital if you choose to participate in this study.

Some subjects who receive 131I-MIBG on this study will also receive only one stem cell transplant instead of two back-to-back stem cell transplants. Subjects who have only one stem cell transplant will get two chemotherapy drugs called busulfan and melphalan (BuMel) instead of the drugs used when two back-to-back transplants are given. BuMel is an accepted transplant chemotherapy regimen in Europe and other parts of the world, but is not part of current COG recommended therapy.

Crizotinib is an experimental anticancer drug that has not been approved by the FDA for use in treating high-risk NBL. Crizotinib has been approved by the FDA for use in treating adults with certain types of lung cancer that has spread. Crizotinib has been well-tolerated in children and adults with cancer. Crizotinib will only be used in subjects whose tumor shows changes in a gene called ALK. Changes in the ALK gene are only found in 10-15% of children with high-risk NBL.

Eligibility

Inclusion Criteria:

  • Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)

  • Patient must be >= 365 days and =< 30 years of age at diagnosis

  • Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:

    • Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:

      • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
      • Age > 547 days regardless of biologic features
    • Patients with INRG stage MS disease with MYCN amplification

    • Patients with INRG stage L2 disease with MYCN amplification

    • Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M

    • Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M

  • Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible

  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:

    • 1 to < 2 years: male = 0.6; female = 0.6
    • 2 to < 6 years: male = 0.8; female = 0.8
    • 6 to < 10 years: male = 1; female = 1
    • 10 to < 13 years: male = 1.2; female = 1.2
    • 13 to < 16 years: male = 1.5; female = 1.4
    • >= 16 years: male = 1.7; female = 1.4
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45

  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram

  • No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure

Exclusion Criteria:

  • Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
  • Patients with bone marrow failure syndromes
  • Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
  • Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation