BLINATUMOMAB for Acute lymphoblastic leukemia

Inclusion criteria

• {"criterion_text":"- newly diagnosed acute lymphoblastic leukemia or\n- newly diagnosed acute undifferentiated leukemia or\n- newly diagnosed mixed phenotype acute leukemia (MPAL) meeting one of the following criteria: • biphenotypic with a dominant T or B lineage assignment • bilineal either with a dominant lymphoblastic population or if another reasonable rationale exists to treat the patient with an ALL-based therapy regimen\n- age < 18 years (up to 17 years and 365 days) at the day of diagnosis\n- patient enrolled in a participating center\n- written informed consent to trial participation and transfer and processing of data"}

Exclusion criteria

• {"criterion_text":"- Ph+ (BCR::ABL1 or t(9;22)-positive) ALL\n- participation in another clinical trial except for ad-on trials within the scope of supportive care approved by the sponsor\n- other condition (either pre-existing or related to leukemia biology as present at diagnosis) or circumstances that significantly conflict with the treatment according to the protocol\n- live vaccine immunization within 2 weeks before start of protocol treatment\n- bilineal leukemia with a lymphoblastic and a separate non-lymphoblastic (≥ 10% of total cells) blast subset\n- pre-treatment with cytostatic drugs\n- glucocorticoid pre-treatment with ≥ 1 mg/kg/d Prednisolone equivalent for more than two weeks during the last month before diagnosis\n- treatment started according to another protocol\n- underlying disease that does not allow treatment according to the protocol\n- ALL diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy\n- evidence of pregnancy or lactation period\n- Sexually active adolescents not willing to use highly effective contraceptive method (Pearl Index <1) until 12 months after end of anti-leukemic therapy"}

Primary endpoints

• {"endpoint_text":"- R-eHR: The primary endpoint will be the time from randomization until the first event defined as follows: • Cytomorphological or molecular non-response (resistance to protocol treatment, considered as event after post-consolidation treatment – HR blocks or blinatumomab therapy), • relapse, • second malignancy or death from any cause. This will be called EFS time.","definition_or_measurement_approach":"Time from randomization to first event (cytomorphological or molecular non-response, relapse, second malignancy, or death). Defined as EFS (event-free survival) time."}
• {"endpoint_text":"- (2a) R-HR: Frequency and incidence of grade 4 adverse events or death from any cause, non-serious adverse events of medical interest during post-consolidation treatment (blinatumomab and HR blocks)","definition_or_measurement_approach":"Frequency and incidence (counts and rates) of grade 4 AEs or deaths and specified non-serious AEs of medical interest during post-consolidation treatment (comparison between blinatumomab and HR blocks)."}
• {"endpoint_text":"- (2a) R-HR: Frequency of MRD-negative patients after first and third cycle of Blinatumomab or after the HR-1’/HR-3’ block compared under non-inferiority assumption","definition_or_measurement_approach":"Proportion of MRD-negative patients measured after first and third blinatumomab cycles or after HR-1'/HR-3' blocks; comparison under a non-inferiority framework."}

Secondary endpoints

• {"endpoint_text":"- (1b) Time from randomization to death from any cause","definition_or_measurement_approach":"Overall survival measured as time from randomization to death from any cause."}
• {"endpoint_text":"- (1c) Frequency and incidence of grade 4 adverse events or death during Consol Bext and after but before 1st day of HR-1` block or 1st blinatumomab cycle.","definition_or_measurement_approach":"Frequency and incidence (counts/rates) of grade 4 AEs or death during extended consolidation (Consol Bext) and the interval before HR-1' block or first blinatumomab cycle."}
• {"endpoint_text":"- (1c, 2a) Frequency and incidence of AE of special interest and SAE in specific protocol phases, randomized arms and overall during follow-up","definition_or_measurement_approach":"Frequency and incidence of AEs of special interest and SAEs by protocol phase, randomized arm, and overall during follow-up."}
• {"endpoint_text":"- (1d) Proportion of children with negative MRD at TP1a and TP2","definition_or_measurement_approach":"Proportion of patients achieving MRD-negativity at predefined time points TP1a and TP2."}
• {"endpoint_text":"- (2b) Absolute difference in MRD load between TP2 and TP after first blinatumomab cycle or HR-1","definition_or_measurement_approach":"Absolute change in MRD load between TP2 and the time point after first blinatumomab cycle or HR-1."}
• {"endpoint_text":"- (2b) Absolute difference in MRD load between TP2 and third Blinatumomab cycle or HR-3`","definition_or_measurement_approach":"Absolute change in MRD load between TP2 and after third blinatumomab cycle or HR-3'."}
• {"endpoint_text":"- (2c) Absolute MRD loads at TP2 and TP HR Blina 1, d29 71, 113 and TP2, TP HR1, TP HR2, TP HR3.","definition_or_measurement_approach":"Absolute MRD measurements at specified timepoints (TP2, and timepoints during blinatumomab/HR treatment) recorded and compared."}
• {"endpoint_text":"- (2d) Time from the first day of first Blinatumomab cycle or HR-1` block to event: death from any cause (for OS), death, relapse, secondary malignancy or molecular non-response for EFS).","definition_or_measurement_approach":"Time-to-event endpoints measured from first day of first blinatumomab cycle or HR-1' block to specified events (for OS and EFS definitions)."}
• {"endpoint_text":"- (1e, 2f) R-eHR, R-HR: appropriately-defined times to events, frequencies of grade 4 adverse events or death and proportion of patients achieving negative MRD at corresponding timepoints.","definition_or_measurement_approach":"Composite outcomes including time-to-event measures, frequencies of grade 4 AEs or death, and proportions achieving MRD-negativity at corresponding timepoints."}

Poland

Earliest CTIS Part Ii Submission Date

09-09-2024

Latest Decision Or Authorization Date

28-10-2024

Processing Time Days

49

Number Of Sites

15

Number Of Participants

874

Primary sponsor

Full Name

Medical University Of Silesia Katowice Poland

Organisation Type

Educational Institution

Country Of Registered Address

Poland