DINUTUXIMAB BETA for Ewing sarcoma

Inclusion criteria

• {"criterion_text":"- Histologically confirmed, newly diagnosed Ewing Sarcoma (m/f/d) or so-called Ewing-like sarcoma (i.e. translocation-positive small blue round cell sarcoma other than Rhabdomyosarcoma) of bone and / or soft tissue with evidence of EWS translocation by fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (RT-PCR), or next-generation sequencing (NGS) assay\n- Availability of fresh frozen tumor tissue for central GD2-detection\n- Age ≥12 months\n- Start of first line treatment according to standard induction treatment (Cycle 1-4: VDC – IE – VDC – IE)\n- Wash-out phase with a minimum of 14 days after the last dose of the last chemotherapy\n- Lansky (<16 years) Performance Score ≥70% or ECOG (≥16 years) ≤ 2\n- Adequate bone marrow function as evidenced by meeting all the following requirements: white blood cell count > 2000/µl, ANC ≥1000 cells/μL (G-CSF allowed), platelet count 75,000 cells/μL without the use of platelet transfusion within the last 2 days, hemoglobin ≥9 g/dL without the use of red blood cell transfusion within the last 2 days\n- Adequate renal function: creatinine clearance or glomerular filtration rate (GFR) > 60 mL/min/1.73 m2\n- Adequate hepatic function as evidenced by meeting all the following requirements: serum total bilirubin ≤1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN\n- Adequate cardiac function: confirmed by echocardiography with a left ventricular ejection fraction (LVEF) of ≥ 50%\n- No known active HIV, HBV, or HCV infection\n- No severe neurological impairment, particularly no motor or sensory deficits, except for neurological deficits caused by Ewing sarcoma\n- Female patients of childbearing potential must present with a negative serum pregnancy test and agree to employ adequate birth control measures for the duration of the study and until 3 months after the end of treatment. Female patients who are lactating must agree to stop breast-feeding from the start of study treatment until 1 month after the end of treatment\n- Patient or their legal representative is willing and able to comply with the requirements of the study protocol\n- High risk stratification (metastatic disease)\n- Centrally confirmed GD2-positive tumor (biopsy of original and/or residual tumor or liquid biopsy in peripheral blood)"}

Exclusion criteria

• {"criterion_text":"- Relapsed or refractory disease state\n- Patients with hypersensitivity against at least one component of the investigational medicinal product\n- Significant illnesses and/or any of the following: significant psychiatric disabilities or uncontrolled seizure disorders; active uncontrolled peptic ulcer disease; clinically significant neurologic deficit or objective peripheral neuropathy; clinically significant, symptomatic fluid in a third space\n- Active and uncontrolled CNS metastases (indicated by clinical symptoms, cerebral edema, corticosteroid and/or anticonvulsant requirement, or progressive disease); for controlled CNS metastases, patient should have been off corticosteroids for at least 28 days without overt evidence of significant neurological deficits prior to enrollment\n- Chronic Grade ≥2 diarrhea\n- Diagnosis of any malignancy other than the disease under study\n- Any other medical or social condition deemed by the Investigator to be likely to interfere with a patient’s ability to cooperate and participate in the study or interfere with the interpretation of the results\n- Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTc >480 msec\n- Active, uncontrolled infection or an unexplained fever >38.5°C which in the Investigator’s opinion might compromise the patient’s participation in the study or affect the study outcome"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the identification of the recommended phase II dose (RP2D) of dinutuximab beta in combination with vincristine, doxorubicin, and cyclophosphamide, as well as ifosfamide and etoposide, based on the evaluation of dose-limiting toxicities (DLTs), overall safety, and tolerability within the study population.","definition_or_measurement_approach":"Identification of RP2D based on evaluation of dose-limiting toxicities (DLTs), overall safety, and tolerability within the study population (dose-finding)."}

Secondary endpoints

• {"endpoint_text":"- Progression-Free Survival (PFS): The time from the start of treatment until the first documented evidence of disease progression or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Time from start of treatment until first documented disease progression or death from any cause."}
• {"endpoint_text":"- Event-Free Survival (EFS): The time from the initiation of treatment to the occurrence of any treatment-related event, including disease progression, relapse, occurrence of a second malignancy, or death from any cause.","definition_or_measurement_approach":"Time from treatment initiation to occurrence of treatment-related event (disease progression, relapse, second malignancy, or death)."}
• {"endpoint_text":"- Duration of Response (DOR): The time from the first documentation of a complete or partial response to the treatment until the first occurrence of disease progression or relapse.","definition_or_measurement_approach":"Time from first documentation of complete or partial response until disease progression or relapse."}

Austria

Earliest CTIS Part Ii Submission Date

04-02-2025

Latest Decision Or Authorization Date

17-02-2025

Processing Time Days

13

Number Of Sites

1

Number Of Participants

1

Czechia

Earliest CTIS Part Ii Submission Date

09-01-2025

Latest Decision Or Authorization Date

12-02-2025

Processing Time Days

34

Number Of Sites

1

Number Of Participants

1

Sweden

Earliest CTIS Part Ii Submission Date

17-01-2025

Latest Decision Or Authorization Date

13-02-2025

Processing Time Days

27

Number Of Sites

1

Number Of Participants

1

Germany

Earliest CTIS Part Ii Submission Date

17-01-2025

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

434

Number Of Sites

13

Number Of Participants

15

Primary sponsor

Full Name

GPOH gGmbH

Organisation Type

Patient organisation/association

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Zentrum fuer Forschungsfoerderung in der Paediatrie GmbH","duties_or_roles":"[1,10,12,5,6,8,9]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Paediatrisches Forschungsnetzwerk gGmbH","duties_or_roles":"[1,10,12,5,6,8,9]","organisation_type":"Laboratory/Research/Testing facility"}