A Phase II Study of Naxitamab Added to Induction Therapy for Subjects With Newly Diagnosed High-Risk Neuroblastoma

  • STATUS
    Recruiting
  • End date
    Sep 18, 2033
  • participants needed
    76
  • sponsor
    Wake Forest University Health Sciences
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Updated on 18 October 2022
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Summary

This is a prospective, multicenter clinical trial in subjects with newly diagnosed high-risk neuroblastoma to evaluate the efficacy and safety of administering naxitamab with standard induction therapy. The initial chemotherapy will include 5 cycles of multi-agent chemotherapy. Naxitamab will be added to all 5 Induction cycles. Subjects with an ALK mutation or amplification will have ceritinib added to their treatment regimen as soon as results are available. We hypothesize that the addition of anti-GD2 therapy to induction chemotherapy will result in improved end of induction responses and improved survival.

Description

This is a prospective, multicenter clinical trial in subjects with newly diagnosed high-risk neuroblastoma to evaluate the efficacy and safety of administering naxitamab with standard induction therapy.

All subjects will be followed for disease response, event free survival, overall survival and toxicity. Extent of disease will be measured and assessed for changes throughout the course of the study. All efficacy analyses will be performed on the evaluable population which will consist of all enrolled subjects (subjects who initiate treatment with naxitamab in combination with GM-CSF plus standard induction therapy) and who have measurable disease at baseline.

The initial chemotherapy Induction regimen will utilize sequential administration of 5 cycles of multi-agent chemotherapy. Naxitamab will be added to all 5 Induction cycles.

Subjects with an activating ALK mutation or ALK amplification will have ceritinib added to their treatment regimen as soon as results are available.

Stem cell mobilization and collection will occur after the 2nd cycle of induction.

Surgical resection of the primary tumor will ideally occur after the 4th cycle of Induction but may be delayed until after the 5th cycle of Induction if medically necessary.

Disease status evaluations will occur at the following time points: (1) pre-treatment, (2) post Cycle 2 Induction (3) Prior to surgical resection (if performed), (4) End of Induction (which includes surgery and 5 cycles of chemotherapy), and (5) End of Additional/Salvage Therapy as needed.

The current standard of care for high-risk neuroblastoma involves 5-7 cycles of induction chemotherapy with surgical removal of the tumor after 4-5 cycles of chemotherapy, followed by high-dose chemotherapy plus autologous stem cell transplant, then radiation to the primary tumor bed, followed by anti-GD2 immunotherapy and cis retinoic acid. This results in a less than 60% disease free survival for high-risk NB, a survival rate that still greatly needs improvement. Two areas in which improvements can be made include: 1) to improve response rate to induction chemotherapy and 2) to improve EFS by improving maintenance therapy to prevent relapse.

We hypothesize that the addition of anti-GD2 therapy to induction chemotherapy will result in improved end of induction responses and improved survival.

Details
Condition High-risk Neuroblastoma
Treatment Ceritinib, Naxitamab
Clinical Study IdentifierNCT05489887
SponsorWake Forest University Health Sciences
Last Modified on18 October 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stages at diagnosis are eligible, if they meet the other specified criteria
Subjects with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) Stage 4 are eligible with the following: i. Age > 18 months (> 547 days) regardless of biologic features or ii. Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or iii. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
Subjects with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following: i. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or ii. Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
Subjects with newly diagnosed neuroblastoma with INSS Stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
Subjects must be age ≤ 21 years at initial diagnosis
Subjects must be >12 months of age at enrollment
Ability to tolerate Peripheral blood stem cell (PBSC) collection: No known contraindication to PBSC collection. Examples of contraindications would include a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
Adequate Cardiac Function Defined As
Shortening fraction of ≥ 27% by echocardiogram, or
Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram
Adequate liver function must be demonstrated, defined as
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
ALT (SGPT) < 5 x upper limit of normal (ULN) for age
Subjects must have adequate renal function defined as a serum creatinine based on
age/gender as follows
Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8
8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
≥ 16 years 1.7 1.4
A negative serum pregnancy test is required for female participants of childbearing
potential (≥13 years of age or after onset of menses)
Both male and female post-pubertal study subjects must be willing to use a highly
effective contraceptive method (i.e., achieves a failure rate of <1% per year when
used consistently and correctly) from the time of informed consent until 6 months
after study treatment discontinuation. Such methods include: combined (estrogen and
progestogen containing) hormonal contraception associated with inhibition of ovulation
(oral, intravaginal, transdermal), progestogen-only hormonal contraception associated
with inhibition of ovulation (oral, injectable, implantable), intrauterine device
(IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion
vasectomized partner, sexual abstinence
Informed Consent: All subjects and/or legal guardians must sign informed written
consent. Assent, when appropriate, will be obtained according to institutional
guidelines

Exclusion Criteria

Subjects who are less than 1 year of age
Subjects who are 12-18 months of age with INSS Stage 4 and all stage 3 subjects with
favorable biologic features (i.e., nonamplified MYCN, favorable pathology, and DNA
index > 1) are not eligible
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 per a low or intermediate risk neuroblastoma regimen (as per
P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification
status and histology
Treatment with immunosuppressive treatment (local steroids excluded) within 4 weeks
prior to enrollment
Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise
intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry <
% and/or abnormal pulmonary function tests if these assessments are clinically
indicated
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study.)
Subjects receiving any investigational drug concurrently
Subjects with any other medical condition, including but not limited to malabsorption
syndromes, mental illness or substance abuse, deemed by the Investigator to be likely
to interfere with the interpretation of the results or which would interfere with a
subject's ability to sign or the legal guardian's ability to sign the informed
consent, and subject's ability to cooperate and participate in the study
Subjects with a significant intercurrent illness (any ongoing serious medical problem
unrelated to cancer or its treatment) that is not covered by the detailed exclusion
criteria and that is expected to interfere with the action of investigational
medicinal products (IMPs) or to significantly increase the severity of the toxicities
experienced from trial treatment
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