Minimal Residual Disease + B-Cell Acute Lymphoblastic Leukemia, Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia
Conditions
Keywords
Blinatumomab, AMG 103, Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia, Minimal Residual Disease Positive B-Cell Precursor Acute Lymphoblastic Leukemia, R/R B-ALL, MRD+ B-ALL
Brief summary
The main objective of this study is to evaluate the safety and efficacy of SC blinatumomab in children below 12 years of age.
Interventions
DRUGBlinatumomab
Blinatumomab will be administered as a SC injection for up to 5 cycles (each cycle will be 35 days).
Sponsors
Amgen
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
28 Days to 4383 Days
Healthy volunteers
No
Inclusion criteria
* Age ≥28 days to \<12 years at the time of informed consent/assent. * Lansky Performance Status (LPS) of ≥ 50%. * 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. * For Phase 2 cohort in participants with MRD+ B-ALL: * Participants with MRD+ B-ALL must have between ≥ 0.1% and \< 5% blasts in the BM. * Prior CD19-directed therapy will be allowed (with demonstrated continued CD19+ expression) if treatment ended \>4 weeks prior to start of protocol therapy and no prior central nervous system (CNS) complications. * Any Philadelphia chromosome-positive (Ph+) participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
Exclusion criteria
* Active ALL in the CNS. * 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. * Isolated EM disease. * Current autoimmune disease or history of autoimmune disease with potential CNS involvement. * Patients with Down Syndrome are not eligible for this study. * Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication. * Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus. * 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. * Allogeneic HSCT within 12 weeks before the start of blinatumomab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Number of Participants who Experienced Dose Limiting Toxicities (DLTs) | Up to 29 days | — |
| Phase 1b: Number of Participants who Experienced Treatment-emergent Adverse Events (TEAEs) | Up to approximately 7 months | — |
| Phase 1b: Number of Participants who Experienced Serious TEAEs | Up to 2 years and 7 months | — |
| Phase 1b: Number of Participants who Experienced Treatment-related TEAEs | Up to approximately 7 months | — |
| Phase 1b: Number of Participants who Experienced AEs of Interest (EOI) | Up to approximately 7 months | — |
| Phase 2; R Cohort: Number of Participants who had Complete Remission/Complete Remission with Partial Hematological Recovery (CR/CRh) Within the First 2 Cycles | Up to 70 days | — |
| Phase 2; M Cohort: Number of Participants who had CR with MRD Negative Response Within the First 2 Cycles | Up to 70 days | MRD negative response = MRD level \< 10\^-4 (0.01%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Number of Participants who had CR/CRh Within the First 2 Cycles | Up to 70 days | — |
| Phase 1b: Number of Participants who had CR Within the First 2 Cycles | Up to 70 days | — |
| 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 | Up to 70 days | — |
| Phase 1b: Number of Participants with a MRD Negative Response Within the First 2 Cycles | Up to 70 days | MRD negative response = MRD level \< 10\^-4 (0.01%). |
| Phase 1b: Duration of Response (DOR) | 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. |
| Phase 1b: Maximum Concentration (Cmax) of Blinatumomab | Up to approximately 7 months | — |
| Phase 1b: Time to Maximum Concentration (Tmax) | Up to approximately 7 months | — |
| Phase 1b: Area Under the Concentration Time Curve (AUC) | Up to approximately 7 months | — |
| Phase 1b: Number of Participants with Anti-blinatumomab Antibodies | Cycle 1, Day 1 and Cycle 2, Day 1 (Cycle Duration = 35 days) | — |
| Phase 2: Number of Participants who had CR/CRh with MRD Negative Response Within the First 2 Cycles | Up to 70 days | MRD negative response = MRD level \< 10\^-4 (0.01%). |
| Phase 2: DOR | 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. |
| Phase 2; R Cohort: Number of participants who had CR Within the First 2 Cycles | Up to 70 days | — |
| Phase 2; R Cohort: Number of participants who had CR/CRh/CRi and Blast Free Hypoplastic or Aplastic BM Within the First 2 Cycles | Up to 70 days | — |
| Phase 2: Overall Survival (OS) | Up to 2 years and 7 months | OS is defined as the time from the first dose until death due to any cause. |
| Phase 2: Number of Participants who Experienced TEAEs, Serious TEAEs, Treatment Related TEAEs and EOIs | Up to 2 years and 7 months | — |
| Phase 2: Blinatumomab Serum Concentrations | Up to 175 days | — |
| Phase 2: Number of Participants with Anti-blinatumomab Antibodies | Cycle 1, Day 1 and Cycle 2, Day 1 (Cycle Duration = 35 days) | — |
| Phase 2; M Cohort: Number of participants who had CR/CRh/CRi and Blast Free Hypoplastic or Aplastic BM with MRD Negative Response Within the First 2 Cycles | Up to 70 days | MRD negative response = MRD level \< 10\^-4 (0.01%). |
Countries
Japan, United States
Contacts
STUDY_DIRECTORMD
Amgen
Outcome results
None listed