bloedkanker Acute lymphocytic leukaemia
Conditions
Interventions
Blinatumomab will be administered as a continuous IV for 28 days per cycle and
AMG 404 will be administered intravenously (IV) over approximately 30 minutes
starting on Day 1 or 11 of Cycle 1 and do
Sponsors
Amgen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • Age >= 18 years at enrollment. • Subjects with B-precursor ALL, with any of the following: -Refractory to primary induction or refractory to salvage therapy. -In untreated first, second or greater relapse or refractory relapse or relapse after salvage therapy -Relapse at any time after allogeneic HSCT: o Relapse is defined as achievement of CR (CR1) during upfront therapy then relapse during or after continuation therapy. o Refractory disease is defined as the absence of CR after standard induction therapy. o Refractory relapse lack of CR after first salvage therapy o Second relapse or later relapse defined as relapse after achieving a second CR (CR2) in first or later salvage. • Greater than or equal to 5% blasts in the BM. • Eastern Cooperative Oncology Group performance status (ECOG PS)
Exclusion criteria
Exclusion criteria: • History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson*s disease, cerebellar disease, organic brain syndrome or psychosis. • Presence of ALL in the CNS (confirmed by presence of blast cells in CSF) or testes. • Isolated extramedullary disease. • Current autoimmune disease or history of autoimmune disease with potential CNS involvement. • Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy. • Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication. • Cancer chemotherapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy) within 14 days prior to study Day 1 with the exception of intrathecal chemotherapy and/or low dose maintenance therapy (eg vinca alkaloids, mercaptopurine, methotrexate, or hydroxyurea). If subject is eligible for pre phase then all low dose chemotherapy with the exception of intrathecal chemotherapy must be discontinued prior to starting pre phase. Tyrosine kinase inhibitors use in patients with Ph+ ALL is allowed. • Immunotherapy (eg rituximab, alemtuzumab) within 4 weeks before start of protocol-specified therapy. Prior treatment (given > 4 weeks prior to protocol therapy) with any CD19-directed therapy (eg, blinatumomab, CD19-directed chimeric antigen receptor T-cell therapy, anti-CD19 antibodies will be allowed). Refer to section 5.2 of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Dose-limiting toxicities (DLT) • Treatment-emergent adverse events (TEAEs), serious TEAEs, treatment-related TEAEs and adverse events of interest (EOI). | — |
Secondary
| Measure | Time frame |
|---|---|
| • CR/CRh* within the first 2 cycles and across all cycles, • CR within the first 2 cycles and across all cycles • Duration of CR • Duration of CR/CRh • Blinatumomab PK parameters • AMG 404 PK parameters • Anti-blinatumomab Antibodies • Anti-AMG 404 antibodies | — |
Countries
Netherlands
Outcome results
None listed