B Cell Precursor Acute Lymphoblastic Leukemia
Conditions
Interventions
Experimental: Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1)
Cohorts of at least 3 adult participants with R/R B-ALL will be treated with escalating doses of blinatumomab to dete
Sponsors
Oda Kazunori
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ph-IIC, Dose Escalation and Dose Expansion: Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years). 2. Ph-IIRa and Ph-IIMa: Aged >= 17 years at time of informed consent. 3. Ph-IIRb and Ph-IIMb: Age >= 12 years and = 0.01% and = 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. 11. Participants aged 16 to = 50%. 12. Participants aged = 50%. 13. Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible. 14. Ph-IIM: BM function as follows: Absolute Neutrophil Count (ANC) >= 500/uL Platelet count >= 50 000/uL (transfusion permitted) Hemoglobin level >= 9 g/dL (transfusion permitted) The above is a summary, other inclusion criteria details may apply.
Exclusion criteria
Exclusion criteria: 1. Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia. If CSF leukemia is present subjects will have to receive intrathecal therapy and have documented negative CSF prior to enrolling. 2. History or presence of clinically relevant CNS pathology (excluding headache) such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis or severe (>=grade 3) CNS events including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR-T) or other T cell engager therapies. 3. Isolated Extramedullary (EM) Disease. 4. For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts. 5. Current autoimmune disease or history of autoimmune disease with potential CNS involvement. 6. Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication. 7. Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance. 8. Testicular leukemia. 9. History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy. 10. Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy. 11. Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions). 12. Immunotherapy within 4 weeks before start of protocol-specified therapy. 13. Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed (with demonstrated continued CD19+ expression), if treatment ended more than 4 weeks prior to start of protocol therapy and no prior CNS complications. 14. Currently receiving treatment in another investigational device or drug study or less than 30 days or 5 half-lives since ending treatment on another investigational device or drug study(ies). 15. Abnormal screening laboratory parameters. 16. Female participant: Pregnant or breastfeeding or planning to become pregnant or donate eggs, or expected to breastfeed during treatment and for 96 hours after the last dose of investigational product (SC blinatumomab). The above is a summary, other exclusion criteria details may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs) [Time Frame: Up to 29 days] 2. Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs) [Time Frame: Up to approximately 28 weeks] 3. Dose Escalation Phase: Number of participants who experience one or more serious TEAEs [Time Frame: Up to approximately 28 weeks] 4. Dose Escalation Phase: Number of participants who experience one or more treatment-related TEAEs [Time Frame: Up to approximately 28 weeks] 5. Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs) of Interest (AEIs) [Time Frame: Up to approximately 28 weeks] 6. Dose Expansion and Phase 2 Ph-IIR cohort: Number of participants who achieve complete remission (CR) / complete remission with partial hematological recovery (CRh) [Time Frame: Up to 10 weeks] 7. Phase 2 Ph-IIC cohort: Maximum concentration (Cmax) of blinatumomab SC1 and SC2 [Time Frame: Up to approximately 4 weeks] 8. Phase 2 Ph-IIC cohort: Average concentration (Cavg) of blinatumomab SC1 and SC2 [Time Frame: Up to approximately 4 weeks] 9. Phase 2 Ph-IIC cohort: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2 [Time Frame: Up to approximately 4 weeks] 10. Phase 2 Ph-IIC cohort: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2 [Time Frame: Up to approximately 4 weeks] 11. Phase 2 Ph-IIM cohort: Number of participants who achieve CR with MRD-negative response [Time Frame: Up to 10 weeks] | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Dose Escalation and Dose Expansion Phase: Minimum concentration over the dosing interval (Cmin) of blinatumomab [Time Frame: Up to approximately 10weeks] 2. Dose Escalation and Dose Expansion Phase: Cmax of blinatumomab [Time Frame: Up to approximately 10 weeks] 3. Dose Escalation and Dose Expansion Phase: Tmax of blinatumomab [Time Frame: Up to approximately 10 weeks] 4. Dose Escalation and Dose Expansion Phase: AUC of blinatumomab [Time Frame: Up to approximately 10 weeks] 5. Dose Escalation Phase and Phase 2 (Ph-IIC cohort): Number of participants who achieve CR/CRh [Time Frame: Up to 10 weeks] 6. Dose Escalation Phase, Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants with incidence of anti-blinatumomab antibody formation [Time Frame: Up to approximately 28 weeks] 7. Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Overall survival (OS) [Time Frame: Up to approximately 2 years] 8. Dose Expansion Phase and Phase 2 (Ph-IIR cohort and Ph-IIC cohort): Duration of response [Time Frame: Up to approximately 2 years] 9. Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Relapse free survival [Time Frame: Up to approximately 2 years] 10. Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more TEAEs [Time Frame:Up to approximately 28 weeks] 11. Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more serious treatment-emergent adverse event [Time Frame: Up to approximately 2 years] 12. Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more treatment-related treatment-emergent adverse events [Time Frame: Up to approximately 28 weeks] 13. Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Numb | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, Israel, Italy, Japan, Mexico, Netherlands, Romania, South Korea, Spain, Turkey, United States
Contacts
Public ContactContact Local
Amgen K.K.
Outcome results
None listed