Trial Title:
Naxitamab Added to Induction for Newly Diagnosed High-Risk Neuroblastoma
NCT ID:
NCT05489887
Condition:
High-risk Neuroblastoma
Conditions: Official terms:
Neuroblastoma
Ceritinib
Conditions: Keywords:
naxitimab
induction
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Naxitamab
Description:
Naxitamab is a humanized (IgG1) anti-GD2 (hu3F8) monoclonal antibody for the treatment of
neuroblastoma, osteosarcoma and other GD2-positive cancers. Naxitamab was granted
accelerated approval by the FDA in 2020 as treatment (in combination with
granulocyte-macrophage colony-stimulating factor - GM-CSF) for pediatric patients at
least one year of age and adult patients with relapsed or refractory high-risk
neuroblastoma in the bone or bone marrow demonstrating a partial response, minor
response, or stable disease to prior therapy
Arm group label:
Subjects with ALK Wildtype or Unknown
Arm group label:
Subjects with ALK aberration
Other name:
Danyelza
Intervention type:
Drug
Intervention name:
Ceritinib
Description:
Ceritinib is an inhibitor that selectively targets the ALK tyrosine kinase
Arm group label:
Subjects with ALK aberration
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. We
hypothesize that the addition of anti-GD2 therapy to induction chemotherapy will result
in improved end of induction responses and improved survival.
Detailed 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.
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.
Criteria for eligibility:
Criteria:
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:
a) 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.
b) 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.
c) 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:
1. Shortening fraction of ≥ 27% by echocardiogram, or
2. Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.
- Adequate liver function must be demonstrated, defined as:
1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
2. 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 0.8 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
< 94% 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.
Gender:
All
Minimum age:
12 Months
Maximum age:
21 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Alabama, Children's Alabama
Address:
City:
Birmingham
Zip:
35201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jennifer Ward, MD
Email:
jennifer.ward@aah.org
Investigator:
Last name:
Rebecca McFall, MD
Email:
Principal Investigator
Facility:
Name:
Arkansas Children's Hospital
Address:
City:
Little Rock
Zip:
72202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Susan Hall
Phone:
501-364-2760
Email:
HallSF@archildrens.org
Investigator:
Last name:
Kevin Bielamowicz, MD
Email:
Principal Investigator
Facility:
Name:
UCSF Benioff Children's Hospital Oakland-
Address:
City:
Oakland
Zip:
94609
Country:
United States
Status:
Recruiting
Contact:
Last name:
Group Contact
Email:
PedOncRschOAK@ucsf.edu
Investigator:
Last name:
Jennifer Michlitsch, MD
Email:
Principal Investigator
Facility:
Name:
Augusta University Health
Address:
City:
Augusta
Zip:
30912
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kimberly Gray
Email:
kigray@augusta.edu
Investigator:
Last name:
Coleen McDonough, MD
Email:
Principal Investigator
Facility:
Name:
Kapiolani Medical Center for Women and Children
Address:
City:
Honolulu
Zip:
96813
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrea Siu, MPH
Phone:
808-535-7169
Email:
andrea.siu@kapiolani.org
Investigator:
Last name:
Randal Wada, MD
Email:
Principal Investigator
Facility:
Name:
Levine Children's Hospital
Address:
City:
Charlotte
Zip:
28204
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Jontyce Green, RN
Phone:
980-442-2356
Email:
jontyce.green@atriumhealth.org
Investigator:
Last name:
Thomas Russell, MD
Email:
Principal Investigator
Facility:
Name:
Wake Forest University Health Sciences
Address:
City:
Winston-Salem
Zip:
27157
Country:
United States
Status:
Recruiting
Contact:
Last name:
Graham Keyes
Email:
grkeyes@wakehealth.edu
Contact backup:
Last name:
L
Investigator:
Last name:
Sarah Supples, MD
Email:
Principal Investigator
Facility:
Name:
Dell Children's Blood and Cancer Center
Address:
City:
Austin
Zip:
78723
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rhea Robinson, RN
Phone:
512-628-1902
Email:
TXAUS-DL-SFCHemonc.research@ascension.org
Investigator:
Last name:
Virginia Harrod, MD
Email:
Principal Investigator
Facility:
Name:
UHC Sainte-Justine
Address:
City:
Montréal
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Guillaume Leblanc
Email:
guillaume.leblanc.hsj@ssss.gouv.qc.ca
Investigator:
Last name:
Pierre Tiera, MD
Email:
Principal Investigator
Facility:
Name:
CHUQ
Address:
City:
Quebec City
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Valérie-Ève Julien
Email:
Valerie-Eve.Julien@crchudequebec.ulaval.ca
Investigator:
Last name:
Bruno Michon, MD
Email:
Principal Investigator
Start date:
September 14, 2022
Completion date:
September 2033
Lead sponsor:
Agency:
Giselle Sholler
Agency class:
Other
Collaborator:
Agency:
Y-mAbs
Agency class:
Other
Source:
Milton S. Hershey Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05489887
http://www.beatcc.org
