Trial Title:
Induction Chemoimmunotherapy for Patients With High-risk Neuroblastoma
NCT ID:
NCT06071897
Condition:
Neuroblastoma
Ganglioneuroblastoma
Conditions: Official terms:
Neuroblastoma
Ganglioneuroblastoma
Antibodies
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
monoclonal antibodies GD2
Description:
Main target of this trial is to estimate tolerability and toxicity of combination of
standard chemotherapy (N5 and N6) with anti-GD2 MAB
N5Q. N5 (see above) Dinutuximab beta 10 mg/m2 i.v., days 5-9*
N6Q. N6 (see above) Dinutuximab beta 10 mg/m2 i.v., days 6-10*
G-CSF (granulocyte colony-stimulating factor) 5 mcg/kg s.c. on day 9 until the ANC is
more than 2000 /ml or until counts have recovered for the next cycle of therapy
Arm group label:
intervention/treatment
Summary:
The modern strategy of therapy of high-risk neuroblastoma, stage 4, consists of three
phases - induction, consolidation and post- consolidation. Still current approaches
demonstrates insufficient levels of ORR (overall response rate), OS (overall survival)
and EFS (event free survival).
NB-HR-2023 (neuroblastoma high risk) protocol aimed to investigate tolerability and
toxicity and potential improvement of ORR, OS and EFS by overcoming of tumor
heterogeneous drug resistance using the synergistic interaction of cytostatic and
immunobiological agents in the induction. Protocol include the combination of standard
chemotherapy (N5 and N6) with anti-GD2 MAB, which is potentially expected to improve
outcomes in patients with high-risk neuroblastoma and ganglioneuroblastoma, 4th stage
older 18 months.
Currently, treatment with combinations of cytostatics with immunobiological agents is
limited due to the risk of complications, which, nevertheless, is controlled with proper
monitoring and concomitant therapy. Still no data about use of combination of standard
chemotherapy (N5 and N6) with ch14.18/CHO MAB (dinutuximab beta) in induction in primary
patients with neuroblastoma.
Prospective, interventional trial include patients with neuroblastoma and
ganglioneuroblastoma, 4th stage of the high-risk group older 18 months, who will receive
combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB.
Consolidation and post consolidation chemotherapy courses are not the subjects for
analysis.
Patients with high-risk neuroblastoma and ganglioneuroblastoma, stage 4, older 18 months
who receive combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB
at the Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology
and Immunology Delayed surgery (if needed) will be done after the 4th or 6th course of
induction therapy and stem cells apheresis after the 2nd-5th course of induction therapy.
Detailed description:
The modern strategy of therapy of high-risk neuroblastoma, stage 4, consists of three
phases - induction, consolidation and post- consolidation. Still current approaches
demonstrates insufficient levels of ORR (overall response rate), OS (overall survival)
and EFS (event free survival). NB-HR-2023 protocol aimed to investigate potential
improvement of ORR, OS and EFS by overcoming of tumor heterogeneous drug resistance using
the synergistic interaction of cytostatic and immunobiological agents in the induction.
Protocol include the combination of standard chemotherapy (N5 and N6) with anti-GD2 MAB,
which is potentially expected to improve outcomes.
Currently, treatment with combinations of cytostatics with immunobiological agents is
limited due to the risk of complications, which, nevertheless, is controlled with proper
monitoring and concomitant therapy. Still no data about use of combination of standard
chemotherapy (N5 and N6) with anti-GD2 MAB in induction.
Main target of this trial is to estimate tolerability and toxicity of combination of
standard chemotherapy (N5 and N6) with anti-GD2 MAB Prospective, interventional trial
include patients with high-risk neuroblastoma and ganglioneuroblastoma, 4th stage older
18 months, who will receive combination of standard induction chemotherapy (N5 and N6)
with anti-GD2 MAB. Consolidation and post-consolidation chemotherapy courses are not the
subjects for analysis.
Patients (n=15) with high-risk neuroblastoma and ganglioneuroblastoma, 4th stage , who
receive combination of standard induction chemotherapy (N5 and N6) with anti-GD2 MAB at
the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology
and Immunology.
Patients to be enrolled should met the eligibility criteria (see below) and will receive
the induction therapy: two courses of standard chemotherapy and four courses of
combination of anti-GD2 МАB ch14.18/CHO (dinutuximab beta).
N5Q cycle: cisplatin (40 mg/m2 per day, IV, in days 1-4) + etoposide (100 mg/m2 per day,
IV, days 1-4) + vincristine (1,5 mg/m2 per day, IV, day 1 + dinutuximab beta (10 mg/m2
per day, IV, Days 5-9) N6Q cycle: vincristine (1.5 mg/m2 per day, IV, days 1, 8) +
dacarbazine (200 mg/m2 per day, IV, days 1-5) + ifosfamide (1500 mg/m2 per day, IV, days
1-5) + doxorubicin (30 mg/m2 per day, IV, days 6, 7) + dinutuximab beta (10 mg/m2 per
day, IV days 6-10).
Delayed surgery (if needed) will be done after the 4th or 6th course of induction therapy
and stem cells apheresis after the 2nd-5th course of induction therapy.
Interim analyses will be carried out in 1, 2 and 3 years from the first patient
enrollement.
The final analysis with the assessment of the ORR, OS, EFS of patients will be carried
out in 1 year and 3 years from the date of inclusion of the last patient in the protocol.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Signed informed consent
- Verified diagnosis of neuroblastoma or ganglioneuroblastoma (ICD-10 codes C47.3,
C47.4, C47.5, C47.6, C47.8, C47.9, C48, C74.1, C74.9, C76.0, C76.1, C76.2, C76.7,
C76.8).
- High-risk patients in accordance with the risk stratification of to the GPOH-NB2004
protocol with stage 4 according to the International Neuroblastoma Staging System
(INSS) from 18 months of life to 18 years.
- ≥ 70% estimation by Lansky or Karnowski scale at the at the start point of
chemoimmunotherapy.
- Life expectancy ≥ 12 weeks from therapy initiation
- No signs of drug-induced neuropathy or neuropathic pain.
- Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase
(AST) activity < 5 values of the upper limit of the norm (VGN).
- Adequate renal function: creatinine clearance or glomerular filtration rate (GFR) >
60 ml/min/1.73 m2.
- Coagulogram parameters: prothrombin index (PTI) 70-120%, activated partial
thromboplastin time (APTT) < 36 s.
- Absence of clinical signs of heart failure, left ventricular ejection fraction
(LVEF) ≥ 55%.
- Assessment of the function of the respiratory system (saturation on the pulse
oximeter > 94% without the use of oxygen, there is no respiratory disturbance at
rest), the absence of pathology during chest X-ray.
Exclusion Criteria:
- Neuroblastoma or ganglioneuroblastoma of the low-risk group or intermediate-risk
group, by NB 2004 protocol and disease staging according to INSS (stages 1-3 and 4s
without apmplification of MYCN gene, stage 4 in patients under 18 months of age) and
high-risk patients with stages 1-3/4s with amplification of MYCN gene.
- Presence in anamnesis of acute intolerance reactions or contraindications to the
main chemotherapeutic, immunobiological agents and any concomitant therapy drugs
used within the framework of this clinical trial protocol.
- Pregnancy due to the high teratogenic activity and toxicity of drugs used in the
clinical trial protocol. A pregnancy test is indicated for patients of childbearing
age.
Gender:
All
Minimum age:
18 Months
Maximum age:
18 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Research Institute of Pediatric Hematology, Oncology and Immunology
Address:
City:
Moscow
Zip:
117997
Country:
Russian Federation
Status:
Recruiting
Contact:
Last name:
Lena Smirnova
Phone:
+7 495 287 65 70
Phone ext:
5551
Email:
lena.smirnova@fccho-moscow.ru
Start date:
September 1, 2023
Completion date:
September 1, 2029
Lead sponsor:
Agency:
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Agency class:
Other
Source:
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06071897
