Acute Lymphoblastic Leukemia in children and adolescents <18 years of age MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Sponsors
Medical University of Silesia
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - newly diagnosed acute lymphoblastic leukemia or - 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 - newly diagnosed acute undifferentiated leukemia - age =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Ph+ (BCR-ABL1 or t (9;22)-positive) ALL - bilineal leukemia with a lymphoblastic and a separate non-lymphoblastic (= 10% of total cells) blast subset - pre-treatment with cytostatic drugs - glucocorticoid pre-treatment with = 1 mg/kg/d Prednisolone equivalent for more than two weeks during the last month before diagnosis - treatment started according to another protocol - underlying diseases that does not allow treatment according to the protocol - ALL diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy - evidence of pregnancy or lactation period - Sexually active adolescents not willing to use highly effective contraceptive method (Pearl index <1) until 12 months after end of anti-leukemic therapy - Participation in another clinical trial except for ad-on trials within the scope of supportive care approved by the sponsor - 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 - Live vaccine immunization within 2 weeks before start of protocol treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: (1a) Randomization R-eHR: In children with early high-risk (early HR) pB-ALL defined by genetics and/or inadequate treatment response over the course of induction: Can the pEFS from time of randomization be improved by additional therapy with the proteasome inhibitor Bortezomib during an extended consolidation treatment phase compared with standard extended consolidation? (2a) Randomization R-HR: In children with high-risk (HR) pB-ALL defined by genetics and/or inadequate treatment response by the end of consolidation: Can the immunotherapy with Blinatumomab (three cycles, 15 µg/m²/d for 28 days per cycle) plus 6 doses intrathecal Methotrexate decrease the frequency of life-threatening treatment-related toxicities without decreasing the frequency of achieving negative MRD compared with standard post-consolidation chemotherapy (HR blocks) regimen? ;Secondary Objective: (1b) eHR randomization: Can the overall survival be improved by the treatment in the experimental arm. (1c) eHR randomization: What is the incidence of treatment-related toxicities and mortality in the experimental arm compared to the standard arm. (1d) eHR randomization: Can the MRD load after consolidation treatment be reduced by the additional treatment with Bortezomib? (2b) R-HR: What is the change of MRD load associated with treatment with blinatumomab compared with standard HR blocks? (2c) R-HR: What are the dynamics of MRD load in children treated with blinatumomab at predefined timepoints compared with those receiving standard high-intensity post-consolidation therapy? (2d) R-HR: What is the proportion of patients with poor response to Blinatumomab as defined in the protocol as compared to the MRD response after the HR-1’ and HR-2’ block in the control arm? (continuation in the second language window);Primary end point(s): (1a) R-eHR : The primary endpoint will be the time from randomization until the first event defined as follows: •Cytomorphological or molecul | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): (1b) Time from randomization to death from any cause (1c) Frequency and incidence of grade 4 adverse events or death during ConsolIBext and after but before 1st day of HR-1` block or 1st blinatumomab cycle. (1c, 2a) Frequency and incidence of AE of interest and SAE in specific protocol phases, randomized arms and overall during follow-up (1d) Proportion of children with negative MRD at TP1a and TP2 (2b) Absolute difference in MRD load between TP2 and TP after first blinatumomab cycle or HR-1 (2b) Absolute difference in MRD load between TP2 and third Blinatumomab cycle or HR-3` (2c) Absolute MRD loads at TP2 and TP HR Blina 1, d29 71, 113 and TP2, TP HR1, TP HR2, TP HR3. (2d) Proportion of children in either arm at TP HR1/HR2 or TP 1 Blina d29/d73 with poor MRD response defined by protocol. (2e) 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). (1e, 2f) R-eHR, R-HR: appropriately-defined times to events, frequencie of grade 4 adverse events or death and proportion of patients achieving negative MRD at corresponding timepoints.;Timepoint(s) of evaluation of this end point: Survival, treatment-related mortality, AE and SAE: end of study MRD related endpoints: after the respective MRD evaluation of the last patient in study | — |
Countries
Poland
Contacts
Public ContactAcademic Research Organization
Clinical Trials Unit at the Medical University of Lodz
Outcome results
None listed