High-Risk NeuroblastomaPhase 1ChIm-NB-PLNCT05272371
Immunotherapy With Dinutuximab Beta in Combination With Chemotherapy for the Treatment of Patients With Primary Neuroblastoma Refractory to Standard Therapy and With Relapsed or Progressive Disease
A Phase 1 study testing Chemoimmunotherapy (Dinutuximab beta in combination with chemotherapy) in people with High-Risk Neuroblastoma, run by Jagiellonian University at 1 site in Poland.
Trial summary
Safety evaluation and initial efficacy evaluation will be conducted in a group of patients as a non-commercial, open-label clinical trial of dinutuximab beta (Qarziba) phase IIa. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- High-Risk Neuroblastoma
- What is being tested?
- Chemoimmunotherapy (Dinutuximab beta in combination with chemotherapy)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 sitePoland
- Study dates
- 1 Dec 2021to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of NBL according to international criteria (International Neuroblastoma Risk Group, INRG).
- Patients 1-18 years of age with HR-NBL with primary refractory disease, disease progression or recurrence.
- Adequate function of vital organs (if abnormal, dysfunction below grade 4 according to the CTC AE WHO classification, except for disorders defined in the exclusion criteria).
- Life expectancy ≥6 months.
- Obtaining the informed written consent of the patient and/or statutory representative for the treatment.
- Female patients of childbearing potential must consent to the use of effective contraception; Breastfeeding patients must consent to the termination of breastfeeding.
- Patients who have previously received immunotherapy with DB or other anti-GD2 specific antibodies may be eligible for this study.
Who cannot join
- Patients with toxicities of ≥3 CTCAE WHO grade, except hearing impairment, hematological disorders, liver and kidney disorders.
- Patients with neurological toxicities of ≥2 CTCAE WHO grade.
- Active life-threatening infection until stabilization of the patient's condition.
- Pregnancy and / or lactation.
- Sexually active patients who refuse to use an effective method of contraception.
- Current treatment with experimental drugs or use of such treatment within 2 weeks before signing the informed consent to participate in the study.
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- Radiotherapy within 3 weeks prior to the start of the study.
- Participation in another clinical trial within 6 months before signing the informed consent to participate in the trial (not applicable to clinical trials in 1st line of treatment in HR-NBL).
- Lack of informed written consent to treatment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Poland1 site, 1 recruiting
- Recruiting
University Children Hospital
Krakow, Malopolska, 30-663
Walentyna Balwierz, Prof., +48123339220, walentyna.balwierz@uj.edu.pl
About this study
Safety evaluation and initial efficacy evaluation will be conducted in a group of patients as a non-commercial, open-label clinical trial of dinutuximab beta (Qarziba) phase IIa.
The investigational medicinal product will be dinutuximab beta (anti-GD2 antibodies against GD2 disialoganglioside on NBL cells) at a dose of 10 mg / m2 / day by continuous infusion for 5 days in combination with irinotecan / temozolomide, topotecan / temozolomide or N5 / N6 chemotherapy GPOH protocol.
Read more
The study group will be patients with recurrent / progression of NBL or disease resistant to first-line treatment, for whom there are currently no standards of management, and the treatment methods used so far do not give a chance to achieve a permanent remission of the disease. After diagnosis of relapse / progression or resistance to treatment, it is permissible to administer 2 cycles of standard chemotherapy prior to enrollment in the study.
The study plans to recruit 20 patients who will receive 5-7 cycles of DB with chemotherapy. The choice of an appropriate chemotherapy regimen will depend on the patient's prior treatment and tolerance.
The safety assessment will be conducted based on the registration of the types and frequency of adverse reactions identified on the basis of the registration of clinical parameters, symptoms and / or diseases reported by the patient or identified during the intervention and / or follow-up visits, abnormal laboratory and / or imaging test results.
The initial assessment of the effectiveness will consist in comparing the percentage of objective responses obtained and the annual EFS and PFS (imaging tests, including scintigraphy, bone marrow examination and tumor markers). The study also included an exploratory evaluation of the usefulness of immunological, genetic and other studies.
Read the detailed description
Neuroblastoma (NBL) accounts for 8-10% of all childhood malignancies. It is the most common solid tumor outside the central nervous system in people <18 years of age. It occurs in 6-11 / 1 million children annually. In Poland, NBL is diagnosed annually in 60-70 patients, in 1/3 high-risk disease (HR). In 90% of children, NBL is diagnosed before the age of 5. The diagnosis is made on the basis of the histopathological assessment of the tumor tissue or the presence of NBL cells in the bone marrow together with elevated levels of catecholamines or their metabolites in the urine. The prognostic factors include the patient's age at diagnosis, stage of disease, tumor histopathology, DNA ploidy, MYCN gene status, chromosomal changes, and initial response to therapy. Due to the different course of the disease, the therapeutic decision is made after determining the risk group based on international criteria (International Neuroblastoma Risk Group Stage System, INRGSS and International Neuroblastoma Staging System, INSS). In the lowest-risk group, management is limited to observation or surgery, and in the intermediate-risk group, only standard low- and intermediate-intensity chemotherapy or combined with radiation therapy and surgery is performed. In contrast, HR-NBL uses intensive combination therapy, including standard induction chemotherapy, surgery, high-dose chemotherapy (HD-CHT) and autologous hematopoietic stem cell transplantation (auto-HSCT), radiotherapy and maintenance therapy with 13-cis retinoic acid and targeted immunotherapy with anti-GD2 antibodies. Treatment outcomes in NBL vary from spontaneous tumor regression in some infants to an OS rate of <50% despite intensive combination therapy in the HR-NBL group.
- Conditions
- High-Risk Neuroblastoma
- Being tested
- Chemoimmunotherapy (Dinutuximab beta in combination with chemotherapy)
- Keywords
- neuroblastoma dinutuksymab beta chemoimmunotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemoimmunotherapy (Dinutuximab beta in combination with chemotherapy)Combination product
Dinutuximab beta in combination with chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Chemoimmunotherapy arm. Receives: Combination Product: Chemoimmunotherapy (Dinutuximab beta in combination with chemotherapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of cycles aborted due to toxicity.
Measured: 12 months after end of treatment.
Number of cycles in which treatment interruptions due to the occurrence of side effects will be longer than provided for in the treatment protocol.
Measured: 12 months after end of treatment.
Number of episodes of Capillary Leak Syndrome, regardless of severity.
Measured: 12 months after end of treatment.
Number of episodes of cytokine release syndrome, regardless of severity.
Measured: 12 months after end of treatment.
Number of episodes of allergic reactions in CTCAE grade 3 and 4 (version in force at that time).
Measured: 12 months after end of treatment.
Number of hematological toxicities in grade 3 and 4 CTCAE (version in force at that time).
Measured: 12 months after end of treatment.
Number of neurological toxicity episodes, regardless of severity.
Measured: 12 months after end of treatment.
The percentage of patients with pupil disorders and / or visual disturbances.
Measured: 12 months after end of treatment.
Proportion of patients with renal or hepatic impairment in CTCAE grade 3 and 4 (version in force at that time).
Measured: 12 months after end of treatment.
Other side effects in grade 3 and 4 CTCAE (version in force at the time)3 and 4 (version in force at that time).
Measured: 12 months after end of treatment.
Secondary outcomes (5)
Percentage of patients with complete remission assessed during the study and at the last visit.
Measured: 12 months after end of treatment.
Percentage of patients with partial remission assessed during the study and at the last visit.
Measured: 12 months after end of treatment.
Percentage of patients with disease stabilization assessed during the examination and at the last visit.
Measured: 12 months after end of treatment.
Percentage of patients PFS assessed during the study.
Measured: 12 months after end of treatment.
Percentage of patients ESF assessed during the study.
Measured: 12 months after end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2022
- Study start1 Dec 2021
- Primary completion30 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-Risk NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Treatment group compared to historical group.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jagiellonian University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Walentyna Balwierz, Jagiellonian University
- Investigators
- Walentyna Balwierz, Prof., Principal investigator, Jagiellonian University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05272371
- Sponsor's protocol ID
- ChIm-NB-PL
- Acronym
- ChIm-NB-PL
- Status last verified
- Mar 2022
- First submitted
- 1 Mar 2022
- Last updated
- 9 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy With Dinutuximab Beta in Combination With Chemotherapy for the Treatment of Patients With Primary Neuroblastoma Refractory to Standard Therapy and With Relapsed or Progressive Disease
- ClinicalTrials.gov ID
- NCT05272371
- Acronym / sponsor ID
- ChIm-NB-PL / ChIm-NB-PL
- Conditions
- High-Risk Neuroblastoma
- Keywords
- neuroblastoma dinutuksymab beta chemoimmunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Jagiellonian UniversityUniversity, hospital or other
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 9 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Safety evaluation and initial efficacy evaluation will be conducted in a group of patients as a non-commercial, open-label clinical trial of dinutuximab beta (Qarziba) phase IIa.
The investigational medicinal product will be dinutuximab beta (anti-GD2 antibodies against GD2 disialoganglioside on NBL cells) at a dose of 10 mg / m2 / day by continuous infusion for 5 days in combination with irinotecan / temozolomide, topotecan / temozolomide or N5 / N6 chemotherapy GPOH protocol.
The study group will be patients with recurrent / progression of NBL or disease resistant to first-line treatment, for whom there are currently no standards of management, and the treatment methods used so far do not give a chance to achieve a permanent remission of the disease. After diagnosis of relapse / progression or resistance to treatment, it is permissible to administer 2 cycles of standard chemotherapy prior to enrollment in the study.
The study plans to recruit 20 patients who will receive 5-7 cycles of DB with chemotherapy. The choice of an appropriate chemotherapy regimen will depend on the patient's prior treatment and tolerance.
The safety assessment will be conducted based on the registration of the types and frequency of adverse reactions identified on the basis of the registration of clinical parameters, symptoms and / or diseases reported by the patient or identified during the intervention and / or follow-up visits, abnormal laboratory and / or imaging test results.
The initial assessment of the effectiveness will consist in comparing the percentage of objective responses obtained and the annual EFS and PFS (imaging tests, including scintigraphy, bone marrow examination and tumor markers). The study also included an exploratory evaluation of the usefulness of immunological, genetic and other studies.
Detailed description
Neuroblastoma (NBL) accounts for 8-10% of all childhood malignancies. It is the most common solid tumor outside the central nervous system in people <18 years of age. It occurs in 6-11 / 1 million children annually. In Poland, NBL is diagnosed annually in 60-70 patients, in 1/3 high-risk disease (HR). In 90% of children, NBL is diagnosed before the age of 5. The diagnosis is made on the basis of the histopathological assessment of the tumor tissue or the presence of NBL cells in the bone marrow together with elevated levels of catecholamines or their metabolites in the urine. The prognostic factors include the patient's age at diagnosis, stage of disease, tumor histopathology, DNA ploidy, MYCN gene status, chromosomal changes, and initial response to therapy. Due to the different course of the disease, the therapeutic decision is made after determining the risk group based on international criteria (International Neuroblastoma Risk Group Stage System, INRGSS and International Neuroblastoma Staging System, INSS). In the lowest-risk group, management is limited to observation or surgery, and in the intermediate-risk group, only standard low- and intermediate-intensity chemotherapy or combined with radiation therapy and surgery is performed. In contrast, HR-NBL uses intensive combination therapy, including standard induction chemotherapy, surgery, high-dose chemotherapy (HD-CHT) and autologous hematopoietic stem cell transplantation (auto-HSCT), radiotherapy and maintenance therapy with 13-cis retinoic acid and targeted immunotherapy with anti-GD2 antibodies. Treatment outcomes in NBL vary from spontaneous tumor regression in some infants to an OS rate of <50% despite intensive combination therapy in the HR-NBL group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Treatment group compared to historical group.
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Combination Product: Chemoimmunotherapy (Dinutuximab beta in combination with chemotherapy)Chemoimmunotherapy arm. |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Diagnosis of NBL according to international criteria (International Neuroblastoma Risk Group, INRG).
- Patients 1-18 years of age with HR-NBL with primary refractory disease, disease progression or recurrence.
- Adequate function of vital organs (if abnormal, dysfunction below grade 4 according to the CTC AE WHO classification, except for disorders defined in the exclusion criteria).
- Life expectancy ≥6 months.
- Obtaining the informed written consent of the patient and/or statutory representative for the treatment.
Key exclusion criteria (9 listed)
- Patients with toxicities of ≥3 CTCAE WHO grade, except hearing impairment, hematological disorders, liver and kidney disorders.
- Patients with neurological toxicities of ≥2 CTCAE WHO grade.
- Active life-threatening infection until stabilization of the patient's condition.
- Pregnancy and / or lactation.
- Sexually active patients who refuse to use an effective method of contraception.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemoimmunotherapy (Dinutuximab beta in combination with chemotherapy)Dinutuximab beta in combination with chemotherapy. | Combination product | Intervention arm |
Primary outcome
Number of cycles aborted due to toxicity.
Time frame: 12 months after end of treatment.
Number of cycles in which treatment interruptions due to the occurrence of side effects will be longer than provided for in the treatment protocol.
Time frame: 12 months after end of treatment.
Number of episodes of Capillary Leak Syndrome, regardless of severity.
Time frame: 12 months after end of treatment.
Number of episodes of cytokine release syndrome, regardless of severity.
Time frame: 12 months after end of treatment.
Number of episodes of allergic reactions in CTCAE grade 3 and 4 (version in force at that time).
Time frame: 12 months after end of treatment.
Number of hematological toxicities in grade 3 and 4 CTCAE (version in force at that time).
Time frame: 12 months after end of treatment.
Number of neurological toxicity episodes, regardless of severity.
Time frame: 12 months after end of treatment.
The percentage of patients with pupil disorders and / or visual disturbances.
Time frame: 12 months after end of treatment.
Proportion of patients with renal or hepatic impairment in CTCAE grade 3 and 4 (version in force at that time).
Time frame: 12 months after end of treatment.
Other side effects in grade 3 and 4 CTCAE (version in force at the time)3 and 4 (version in force at that time).
Time frame: 12 months after end of treatment.
5 secondary outcomes
Percentage of patients with complete remission assessed during the study and at the last visit.
Time frame: 12 months after end of treatment.
Percentage of patients with partial remission assessed during the study and at the last visit.
Time frame: 12 months after end of treatment.
Percentage of patients with disease stabilization assessed during the examination and at the last visit.
Time frame: 12 months after end of treatment.
Percentage of patients PFS assessed during the study.
Time frame: 12 months after end of treatment.
Percentage of patients ESF assessed during the study.
Time frame: 12 months after end of treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Walentyna Balwierz, Prof. principal investigator
Jagiellonian University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Chemoimmunotherapy (Dinutuximab beta in combination with chemotherapy) in people with High-Risk Neuroblastoma, run by Jagiellonian University at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Walentyna Balwierz, Prof. (+48 12 333 92 20, walentyna.balwierz@uj.edu.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of cycles aborted due to toxicity. (time frame: 12 months after end of treatment.). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2022.