R/R B-Cell Precursor Acute Lymphoblastic Leukemia MRD+ B-Cell Acute Lymphoblastic Leukemia
Conditions
Interventions
Experimental: Phase 1b: R/R B-ALL
- Participants with R/R B-ALL will receive blinatumomab as SC injection to determine the pediatric recommended Phase 2 dose (RP2D).
- Interventions: Drug: Blinatumo
Sponsors
Oda kazunori
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >= 28 days to = 50%. 3. For Phase 1b and Phase 2 cohort in participants with R/R B-ALL: - Participants with B-ALL relapsed after or refractory to any line of treatment including allogeneic hematopoietic stem cell transplant (HSCT). - Greater than or equal to 5% blasts in the bone marrow (BM) is considered as relapse in the BM. 4. For Phase 2 cohort in participants with MRD+ B-ALL: - Participants with MRD+ B-ALL must have between >= 0.1% and 4 weeks prior to start of protocol therapy and no prior central nervous system (CNS) complications. 6. Any Philadelphia chromosome-positive (Ph+) participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
Exclusion criteria
Exclusion criteria: 1. Active ALL in the CNS. 2. History or presence of clinically relevant CNS pathology or event such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis, or severe (>= grade 3) CNS events including immune effector cell-associated neurologic syndrome (ICANS) from prior CAR-T or other T-cell engager therapies. 3. Isolated EM disease. 4. Current autoimmune disease or history of autoimmune disease with potential CNS involvement. 5. Patients with Down Syndrome are not eligible for this study. 6. Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication. 7. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus. 8. Presence of an acute or uncontrolled chronic infection, or any other concurrent disease or medical condition that could be worsened by the treatment or interfere with the participant's ability to comply with the study protocol. 9. Allogeneic HSCT within 12 weeks before the start of blinatumomab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Phase 1b: Number of Participants who Experienced Dose Limiting Toxicities (DLTs) [Time Frame: Up to 29 days] 2. Phase 1b: Number of Participants who Experienced Treatment-emergent Adverse Events (TEAEs) [Time Frame: Up to approximately 7 months] 3. Phase 1b: Number of Participants who Experienced Serious TEAEs [Time Frame: Up to 2 years and 7 months] 4. Phase 1b: Number of Participants who Experienced Treatment-related TEAEs [Time Frame: Up to approximately 7 months] 5. Phase 1b: Number of Participants who Experienced AEs of Interest (EOI) [Time Frame: Up to approximately 7 months] 6. Phase 2; R Cohort: Number of Participants who had Complete Remission/Complete Remission with Partial Hematological Recovery (CR/CRh) Within the First 2Cycles [Time Frame: Up to 70 days] 7. Phase 2; M Cohort: Number of Participants who had CR with MRD Negative Response Within the First 2 Cycles [Time Frame: Up to 70 days] - MRD negative response = MRD level < 10^-4 (0.01%). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Phase 1b: Number of Participants who had CR/CRh Within the First 2 Cycles [Time Frame: Up to 70 days] 2. Phase 1b: Number of Participants who had CR Within the First 2 Cycles [Time Frame: Up to 70 days] 3. Phase 1b: Number of Participants who had CR/CRh/Complete Remission with Incomplete Hematological Recovery (CRi) or Blast Free Hypoplastic or Aplastic Bone Marrow (BM) Within the First 2 Cycles [Time Frame: Up to 70 days] 4. Phase 1b: Number of Participants with a MRD Negative Response Within the First 2 Cycles [Time Frame: Up to 70 days] - MRD negative response = MRD level < 10^-4 (0.01%). 5. Phase 1b: Duration of Response (DOR) [Time Frame: Up to 2 years and 7 months] - DOR is defined as the time from the first response of CR/CRh within the first 2 cycles until hematological relapse (Including extramedullary [EM] relapse) per investigator's assessment or death due to any cause, whichever occurs first. 6. Phase 1b: Maximum Concentration (Cmax) of Blinatumomab [Time Frame: Up to approximately 7 months] 7. Phase 1b: Time to Maximum Concentration (Tmax) [Time Frame: Up to approximately 7 months] 8. Phase 1b: Area Under the Concentration Time Curve (AUC) [Time Frame: Up to approximately 7 months] 9. Phase 1b: Number of Participants with Anti-blinatumomab Antibodies [Time Frame: Cycle 1, Day 1 and Cycle 2, Day 1 (Cycle Duration = 35 days)] 10. Phase 2: Number of Participants who had CR/CRh with MRD Negative Response Within the First 2 Cycles [Time Frame: Up to 70 days] - MRD negative response = MRD level < 10^-4 (0.01%). 11. Phase 2: DOR [Time Frame: Up to 2 years and 7 months] - DOR is defined as the time from the first response of CR/CRh within the first 2 cycles until hematological relapse (Including EM relapse) per investigator's assessment or death due to any cause, whichever occurs first. 12. Phase 2; R Cohort: Number of participants who had CR Within the First 2 Cycles [Time Frame: Up to 70 days] 13. Phase 2; R Cohort: Number of participants who had CR/CR | — |
Countries
Japan, United States
Contacts
Public ContactContact Local
Amgen K.K.
Outcome results
None listed