Naxitamab added to standard induction therapy for newly diagnosed high-risk neuroblastoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 2 trial uses a backbone similar to the St. Jude NB2012/ANBL1531 protocols and replaces hu14.18K322A with Naxitamab during Induction Cycles 1-5. Participants receive COG-type induction therapy with Naxitamab and GM-CSF, followed by physician-directed consolidation, radiation, and post-consolidation therapy as needed. Patients are assessed before enrollment, after two cycles, and after chemotherapy to determine response, with progression or less-than-partial response leading to protocol discontinuation. Follow-up visits occur post-surgery and every four months for five years from diagnosis to monitor outcomes and safety.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Age - 12 months to 21 years at protocol enrollment
* Clinical eligibility criteria:

  1. Newly diagnosed high risk neuroblastoma.
  2. BOTH stage M (INRG - International Neuroblastoma Risk Group) and age ≥547 days.
  3. Patients ≥ 547 days of age who were initially diagnosed with INRG L1 or L2 disease but progress to Stage M without chemotherapy
  4. Patients \< 547 days of age with INRG Stage M or MS disease and patients of any age with INRG L2 with MYCN amplification (v-myc avian myelocytomatosis viral related oncogene)
* Pathology:

  1. Neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis, or
  2. demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines
* Molecular testing:

  1. MYCN testing will be done by FISH (Fluorescence In Situ Hybridization) assessment of the FFPE (Formalin-Fixed Paraffin-Embedded) material submitted from the tumor mass. \> 4-fold increase in MYCN signals as compared to reference signals will qualify as MYCN amplified.
  2. ONCOMINE testing will evaluate ALK (Anaplastic Lymphoma Kinase) mutation
* Timing of patient enrollment

  1. Patients will be enrolled up to 6 weeks from primary diagnosis
  2. Pre-study imaging tests are acceptable up to 3 weeks prior to study enrollment and only if done after any pre-protocol chemotherapy.
* Pre-treatment functional status:

  1. No active bacterial infection without adequate antibiotic therapy
  2. No uncontrolled viral infection - decision will be made after infectious disease consultation
  3. No uncontrolled organ dysfunction:

  i. Renal function based on the Schwartz formula (Schwartz et al. J. Peds, 106:522, 1985). If creatinine level is abnormal chemotherapy treatment will be planned in consultation with Nephrology service. Naxitamab will be initiated if creatinine level is up to 1.2 of normal.

ii. Adequate liver function defined as: -

1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age,
2. and SGPT (Serum Glutamic Pyruvic Transaminase - ALT) ≤ 10 x ULN\* iii. Adequate cardiac function defined as: -

1\. Shortening fraction of ≥ 27% by echocardiogram, 2. or Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram.

Exclusion Criteria:

* Subjects who have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy.
* This will not restrict the emergency regimen at initial diagnosis.
* Patients who are 365-546 days of age with INRG Stage M and MYCN non-amplified NBL, irrespective of additional biologic features.
* Patients ≥547 days of age with INRG Stage L2, MYCN non-amplified NBL, regardless of additional biologic features.
* Patients with known bone marrow failure syndromes.
* Patients on chronic immunosuppressive medications (e.g., tacrolimus, cyclosporine, corticosteroids) for reasons other than prevention/treatment of allergic reactions and adrenal replacement therapy are not eligible. Topical and inhaled corticosteroids are acceptable.
* Patients with a primary immunodeficiency syndrome who require ongoing immune globulin replacement therapy.
* 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 prior to enrollment 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.

Where it's running

• Shaare Zedek Medical Center
  Jerusalem, Israel Recruiting

Study contacts

• Principal investigator: Iris Fried, MD — Shaare Zedek Medical Center
• Study coordinator: Dr. Iris Fried
• Email: irisf@szmc.org.il
• Phone: 00972 508573151

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Supportive care intervention for low-income children with high-risk neuroblastoma

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.