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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05327894
Other study ID # 2021-000213-16
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date December 15, 2022
Est. completion date September 2030

Study information

Verified date April 2024
Source Princess Maxima Center for Pediatric Oncology
Contact Lieke van den Wildenberg
Phone 0031 88 972 72 72
Email trialmanagement@prinsesmaximacentrum.nl
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study is a treatment protocol with blinatumomab for infants under 1 year old who are diagnosed with acute lymphoblastic leukemia with a specific unfavorable genetic alteration. The purpose of the study is to improve the outcome of this disease in infants.


Description:

All infants that are eligible for this study and for whom the parents/legal representatives give informed consent will be enrolled in this study. All patients will receive one cycle of blinatumomab on top of the standard treatment backbone after induction therapy. Medium risk patients, that respond well to the 1st cycle will be treated with a 2nd cycle of blinatumomab replacing one chemo course after consolidation therapy. If they do not respond well enough they will be treated according to the current treatment standard. Minimal residual disease will be used to determine the response to blinatumomab. High risk patients will be eligible for allogeneic stem cell transplantation after the first blinatumomab cycle if they are Minimal Residual Disease (MRD) negative (defined as < 0.01%). Also medium risk patients with insufficient MRD response after induction or after the 1st cycle of blinatumomab will be allocated to high risk treatment and will be eligible for allogeneic stem cell transplantation.


Recruitment information / eligibility

Status Recruiting
Enrollment 160
Est. completion date September 2030
Est. primary completion date September 2027
Accepts healthy volunteers No
Gender All
Age group 1 Day to 365 Days
Eligibility Inclusion Criteria: 1. Patients with newly diagnosed B- precursor acute lymphoblastic leukemia (ALL) or B- cell mixed phenotype acute leukemia (MPAL) according to the World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017, with KMT2A-rearrangement. 2. =365 days of age at time of diagnosis of ALL 3. Written informed consent of the parents or other legally authorized guardian of the patient according to local law and regulations. Exclusion Criteria: 1. KMT2A-germline patients 2. T-ALL 3. Age > 365 days at the time of diagnosis 4. Relapsed ALL 5. Treatment with systemic corticosteroids (equivalent prednisone >10 mg/m2/day) for more than one week and/or any chemotherapeutic agent in the 4-week interval prior to diagnosis. Patients who received corticosteroids by aerosol are eligible for the study. Additional exclusion criteria for blinatumomab: 1. CD19 negative B-precursor ALL at diagnosis 2. CNS involvement (CNS2/CNS3 status) at the EOI. Patients with CNS disease at the time of diagnosis are eligible if CNS1 status is achieved prior to the start of the first blinatumomab cycle (lumbar puncture at ~day 33 of induction). 3. Proven hypersensitivity to the active substance or any of the excipients in blinatumomab. 4. Patients who have received a live vaccine 28 days prior to blinatumomab administration or plan to receive a live vaccine prior to B-cell recovery after the last dose of blinatumomab. If exclusion criteria for blinatumomab are met, the patient should be treated according to the protocol but without blinatumomab.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Blinatumomab
1st cycle: 15 µg/m2/day as a 4 week continuous IV infusion for patients with a M1 marrow. For patients with a M2/M3 marrow a step-dosing strategy is required with a dose of 5 µg/m2/day in week 1 followed by 15 µg/m2/day in weeks 2, 3, and 4.
Blinatumomab
2nd cycle: 15 µg/m2/day as a 4 week continuous iv infusion

Locations

Country Name City State
Argentina Hospital de Pediatría S.A.M.I.C. "Juan P. Garrahan" Buenos Aires
Australia Australian and New Zealand Children's Haematology/Oncology Group Clayton Victoria
Austria St. Anna Children's Hospital Vienna
Belgium Hôpital Universitaire des Enfants Reine Fabiola Brussel
Czechia Hospital Motol V Uvalu 841 Prague
Denmark AUH Skejby Aarhus
Denmark Copenhagen-Rigshospitalet Copenhagen
Denmark Odense University Hospital Odense
Finland New Children's Hospital Helsinki
Finland Kuopio University Hospital Kuopio
Finland Oulu University Hospital Oulu
Finland Tampere University Hospital Tampere
France Hôpital Robert Debré, APHP Paris
Germany Universtitätsklinikum Eppendorf Hamburg
Hungary University of Pécs Pécs
Ireland National Children's Cancer Service Dublin
Italy IRCCS Ospedale Pediatrico Bambino Gesù Roma
Japan Osaka University Graduate School of Medicine 2-2 Osaka
Netherlands Princess Máxima Center for pediatric oncology Utrecht
Norway St. Olavs Hospital Trondheim
Portugal Instituto Portugues de Oncologica Lisboa Lisboa
Saudi Arabia King Abdulaziz Medical City, King Abdullah International Medical Research Center Riyadh
Sweden Childrens Cancer Center Queen Silvia Children´s Hospital, Sahlgrenska University Hospital Gothenburg

Sponsors (3)

Lead Sponsor Collaborator
Princess Maxima Center for Pediatric Oncology Amgen Europe B.V, University of Milano Bicocca

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Ireland,  Italy,  Japan,  Netherlands,  Norway,  Portugal,  Saudi Arabia,  Sweden, 

Outcome

Type Measure Description Time frame Safety issue
Primary Event free survival (EFS). The primary endpoint is EFS, defined as the time from diagnosis to resistance to induction, relapse, death from any cause or second malignancy (whichever occurs first), or time to last follow-up (censored) for patients without events. 5 years
Secondary Overall survival The endpoints for analysis by risk group will be EFS, cumulative incidence (or percentage) of resistance to induction, cumulative incidence of relapse (CIR), death in complete remission (CR) and second malignancy. 8 years
Secondary Endpoints by risk group The endpoints for analysis by risk group will be EFS, cumulative incidence (or percentage) of resistance to induction, cumulative incidence of relapse (CIR), death in complete remission (CR) and second malignancy. 8 years
Secondary Outcome for the entire study cohort and according to risk group Outcome for the entire study cohort and according to risk group will be evaluated in terms of the protocol specific definition of EFS follows: the time from diagnosis to, resistance to proto-col, relapse, death from any cause or second malignancy (whichever occurs first), or time to last follow-up for patients without events. Cumulative incidence (or percentage) of resistance, CIR, death in CR and second malignancy will also be estimated. 8 years
Secondary Minimal Residual Disease MRD response as defined in the protocol and frequencies of MRD levels 8 years
Secondary CD19 (cluster of differentiation antigen 19) negative relapse Proportion of CD19 negative relapses in the entire study cohort and according to risk group 8 years
Secondary Myeloid lineage switches Proportion of myeloid lineage switches in the entire study cohort and according to risk group 8 years
Secondary Grade =3 adverse event Proportion of grade =3 adverse event (AEs) during the blinatumomab course(s). Proportion of adverse events of special interest (AESIs) and serious adverse events (SAEs) in all protocol phases. 8 years
Secondary Grade =2 cardiac disorders Proportion of grade =2 cardiac disorders at 2 and 5 years after diagnosis 5 years
Secondary Overall survival after 1st relapse Overall survival (OS) after first relapse, defined as the time from first relapse to death from any cause, in the entire study cohort and according to risk group 8 years
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