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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Uniwersytet Jagiellonski Collegium Medicum

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 May 2024 → ongoing

Decision date (initial)

2024-05-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-513141-37-00

EudraCT number

2021-003832-96

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of the study is to evaluate the safety profile of 20 patients receiving dinutuximab beta in combination with chemotherapy compared to historical data from two reference groups:
- group 1 for patients treated with chemotherapy without immunotherapy
- group 2 for patients treated with immunotherapy without chemotherapy in patients with relapsed or progressive or primary resistance to treatment.
The reference groups will consist of 2 groups of 10 patients who meet the inclusion criteria for the target group, but are treated only with chemotherapy (reference group 1) or only with immunotherapy (reference group 2) at the Department of Pediatric Oncology and Hematology in Krakow.

Secondary objectives 1

1. The secondary objective of the study is an initial efficacy assessment as a percentage of patients: 1.complete remission assessed during the study and at the last visit, 2.with partial remission assessed during the study and at the last visit, 3.with disease stabilization assessed during the examination and at the last visit, 4. PFS assessed during the study, 5. ESF assessed during the study. In addition, the tertiary and exploratory objective of the study is to evaluate the usefulness of laboratory parameters in predicting response to dinutuximab beta therapy. Tertiary goals will not be subject to formal analysis

Conditions and MedDRA coding

Recurrent or progression of neuroblastoma or neuroblastoma or neuroblastoma refractory to first-line treatment.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Diagnosis of NBL according to international criteria (International Neuroblastoma Risk Group, INRG).
2. Patients 1-18 years of age with HR-NBL with primary refractory disease, disease progression or recurrence.
3. 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).
4. Life expectancy ≥6 months.

Exclusion criteria 5

1. Patients with toxicities of ≥3 CTCAE WHO grade, except hearing impairment, hematological disorders, liver and kidney disorders.
2. Patients with neurological toxicities of ≥2 CTCAE WHO grade.
3. Active life-threatening infection until stabilization of the patient's condition.
4. Pregnancy and / or lactation
5. Radiotherapy within 3 weeks prior to the start of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 10

1. number of cycles aborted due to toxicity
2. number of cycles in which treatment interruptions due to the occurrence of side effects will be longer than provided for in the treatment protocol
3. number of episodes of Capillary Leak Syndrome, regardless of severity
4. number of episodes of cytokine release syndrome, regardless of severity
5. number of episodes of allergic reactions in CTCAE grade 3 and 4 (version in force at that time)
6. number of hematological toxicities in grade 3 and 4 CTCAE (version in force at that time)
7. Number of neurological toxicity episodes, regardless of severity
8. the percentage of patients with pupil disorders and / or visual disturbances
9. proportion of patients with renal or hepatic impairment in CTCAE grade 3 and 4 (version in force at that time)
10. Other side effects in grade 3 and 4 CTCAE (version in force at the time)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Uniwersytet Jagiellonski Collegium Medicum

Sponsor organisation

Uniwersytet Jagiellonski Collegium Medicum

Address

Ul. Sw. Anny 12

City

Cracow

Postcode

31-008

Country

Poland

Scientific contact point

Organisation

Uniwersytet Jagiellonski Collegium Medicum

Contact name

prof. Walentyna Balwierz

Public contact point

Organisation

Uniwersytet Jagiellonski Collegium Medicum

Contact name

prof. Marek Sanak

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications