acute lymphoblastic leukemia in children and adolescents <18 years of age
Conditions
Interventions
Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Current Sponsor code: DEXA
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DEXAMETHASONE
CAS Number
Sponsors
Universitätsklinikum Schleswig-Holstein, Campus Kiel
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 that interferes with the protocol - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Randomization R-eHR: 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 to standard extended consolidation? - Randomization R-HR: High-risk (HR) pB-ALL defined by genetics and/or inadequate treatment response by the end of consolidation: Can the pEFS from time of randomization be improved by a treatment concept including two cycles of post-consolidation immunotherapy with Blinatumomab (15 µg/m²/d for 28 days per cycle) plus 4 doses intrathecal Methotrexate compared to two conventional highly intensive chemotherapy courses? (continued in field for another language) ;Secondary Objective: - All randomizations: Can the overall survival be improved by the treatment in the experimental arm? - All randomizations: What is the incidence of treatment-related toxicities and mortality in the experimental arm compared to the standard arm? - Randomization R-eHR: Can the MRD load after consolidation treatment be reduced by the additional treatment with Bortezomib? - Randomization R-HR: Can treatment-related life-threatening complications and mortality during the intensified consolidation phase of high-risk treatment be reduced when replacing two intensive chemotherapy courses by two cycles of immunotherapy with Blinatumomab? (continued in field for another language) ;Primary end point(s): For the randomized study questions, the primary endpoint will be the time from randomization until the first event defined as follows: Randomization R-eHR, R-HR and R-T: Cytomorphological or molecular non-response (resistance to protocol treatment, considered as event at day zero), relapse, second malignancy or death from any cause. This will be called EFS time. Randomization R-MR: Relapse, second malignancy or death from any cause. This w | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Survival starting at the same time point as the EFS/DFS - Frequency and incidence of treatment-related mortality in induction or CCR - Frequency and incidence of AE of interest and SAE in specific protocol phases, randomized arms and overall during follow-up - MRD load after the randomized treatment phases (R-eHR, R-HR, R-MR and R-T) - MRD load after the first/second cycle of Blinatumomab or after the HR 2’/HR 3’ block (R-HR) - Proportion of patients with poor MRD response to the first Blinatumomab cycle (“Blinatumomab Poor-Response”) (R HR) ;Timepoint(s) of evaluation of this end point: Survival, treatment-related mortality, AE and SAE: end of study MRD related endpoints: after the repective MRD evaluation of the last patient in study | — |
Countries
Australia, Austria, Czechia, Czech Republic, Germany, Israel, Italy, Slovakia, Switzerland
Contacts
Public ContactStudy Coordinator
Universitätsklinikum Schleswig-Holstein, Campus Kiel
Outcome results
None listed