The main objective of this trial is to demonstrate that subcutaneous (SC) blinatumomab in conjunction with chemotherapy (Arm B) is non-inferior to continuous intravenous infusion (cIV) blinatumomab in conjunction with chemotherapy (Arm A) in overall survival (OS) in newly diagnosed participants with Philadelphia chromosome (Ph) negative B-cell precursor acute lymphoblastic leukemia (B-ALL) who are in complete remission (CR) or CR with incomplete peripheral count recovery (CRi) after induction.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
560
Blinatumomab will be administered as a SC injection.
Blinatumomab will be administered as a cIV infusion.
HyperCVAD will administer as the chemo regimen as part of the standard of care (SOC) regimen.
Overall Survival (OS)
Time frame: Up to 5 years from randomization
Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs)
Number of participants who experience TEAEs, serious TEAEs, treatment-related adverse events, and adverse events of interest.
Time frame: Up to 5 years from randomization
Area Under the Concentration-time Curve in Cycle 1 (AUCcycle 1) for SC Blinatumomab
Time frame: Up to Cycle 1 Day 35 (Cycle length = 35 days)
AUCcycle 1 for cIV Blinatumomab
Time frame: Up to Cycle 1 Day 35 (Cycle length = 35 days)
Average Concentration Following Cycle 1 Day 19 Dosing (Cavgd19dose) for SC Blinatumomab
Time frame: From predose on Cycle 1 Day 19 to predose on Cycle 1 Day 22 (Cycle length = 35 days)
Steady-state Concentration (Css) for cIV Blinatumomab
Time frame: Up to Cycle 1 Day 29 (Cycle length = 35 days)
Relapse-free Survival (RFS)
RFS is defined as time from randomization until relapse, death from any cause or measurable residual disease (MRD) non-response, whichever is earlier.
Time frame: Up to 5 years from randomization
Number of Participants With CR With MRD Response
CR with MRD response is defined as MRD \<10\^-4. CR with MRD response is defined as \<5% bone marrow (BM) blasts by cytomorphology with full recovery of peripheral blood counts (absolute neutrophil count \[ANC\] \>1000/µl and platelets \>100,000/µl) and MRD \< 10\^4 and no evidence of extramedullary disease (EMD).
Time frame: Up to 5 years from randomization
Number of Participants With Deep CR With MRD Response
Deep CR with MRD response is defined as MRD \<10\^-6. Deep CR with MRD response is defined as \<5% BM blasts by cytomorphology with full recovery of peripheral blood counts (ANC \> 1000/µl and platelets \> 100,000/µl) and MRD ≤ 10\^6 and no evidence of extramedullary disease.
Time frame: Up to 5 years from randomization
Change from Day 1 Consolidation Cycle 1 to End of Consolidation in Role Functioning as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Time frame: Consolidation Cycles 1, 2, 5 and 6 Day 1 (Cycles length=35 days); Consolidation Cycles 3, 4, 7 and 8 Day 15 (Cycles length=2-4 weeks); Maintenance Cycle 1 Day 1 (Cycle length=28 days)
Change from Day 1 Consolidation Cycle 1 to End of Consolidation in Overall Quality of Life as Measured by EORTC QLQ-C30
Time frame: Consolidation Cycles 1, 2, 5 and 6 Day 1 (Cycles length=35 days); Consolidation Cycles 3, 4, 7 and 8 Day 15 (Cycles length=2-4 weeks); Maintenance Cycle 1 Day 1 (Cycle length=28 days)
Change from Day 1 Consolidation Cycle 1 to End of Consolidation in All Other Domains/Items as Measured by EORTC QLQ-C30
Time frame: Consolidation Cycles 1, 2, 5 and 6 Day 1 (Cycles length=35 days); Consolidation Cycles 3, 4, 7 and 8 Day 15 (Cycles length=2-4 weeks); Maintenance Cycle 1 Day 1 (Cycle length=28 days)
Change From Day 1 Consolidation Cycle 1 to End of Consolidation in the Visual Analogue Scale (VAS)
Change in the VAS will be measured from European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L).
Time frame: Consolidation Cycles 1, 2, 5 and 6 Day 1 (Cycles length=35 days); Consolidation Cycles 3, 4, 7 and 8 Day 15 (Cycles length=2-4 weeks); Maintenance Cycle 1 Day 1 (Cycle length=28 days)
Percentage of Time on Treatment With High Side Effect Bother From Consolidation Cycle 1 to End of Consolidation
Percentage of time on treatment with high side effect bother (score 3-4) from consolidation cycle 1 to end of consolidation will be measured by Functional Assessment of Chronic Illness Therapy (FACIT) GP5.
Time frame: Consolidation Cycle 1 up to Day 8 and then weekly until end of Consolidation Cycle (Cycle length = 35 days)
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