B Cell Precursor Acute Lymphoblastic Leukemia
Conditions
Keywords
R/R B-ALL, MRD+ B-ALL, Relapsed, Refractory, Minimal Residual Disease, AMG 103, Blinatumomab, Acute lymphoblastic leukemia, Adolescent, Adult
Brief summary
The Phase I part of the study aims to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) blinatumomab for treatment of Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL), to determine the maximum tolerated dose (MTD), and recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab. The Phase II part of the study will evaluate the safety, efficacy, and tolerability of SC blinatumomab for treatment of R/R B-ALL and Minimum Residual Disease Positive (MRD+) B-ALL in participants 12 years old and greater. It will also conduct a clinical pharmacokinetic (PK) evaluation of SC1 and SC2 blinatumomab formulations.
Interventions
DRUGBlinatumomab
Blinatumomab will be administered as a subcutaneous (SC) injection.
Sponsors
Amgen
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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). * Ph-IIRa and Ph-IIMa: Aged ≥ 17 years at time of informed consent. * Ph-IIRb and Ph-IIMb: Age ≥ 12 years and \< 17 years at time of informed consent. * Ph-IIR, Ph-IIC, Dose escalation, Dose Expansion: Participants with R/R B-precursor ALL. * Relapsed or Refractory B-precursor ALL at any time after first salvage therapy. * Relapsed B-precursor ALL at any time after allogenic hematopoietic stem cell transplant (HSCT). * Ph-IIR, Ph-IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the Bone Marrow per local assessment. * Ph-IIM: B-precursor ALL and bone marrow blasts (BMB) ≥ 0.01% and \< 5% per local assessment. * Ph-IIM: Availability of an appropriate archival BM specimen from initial or relapse diagnosis and the screening BM sample. * Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. * Participants aged 16 to \< 18 years old: Karnofsky Performance Score ≥ 50%. * Participants aged \< 16 years old: Lansky Performance Score ≥ 50%. * Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible. * Ph-IIM: BM function as follows: * Absolute Neutrophil Count (ANC) ≥ 500/μL * Platelet count ≥ 50 000/μL (transfusion permitted) * Hemoglobin level ≥ 9 g/dL (transfusion permitted) The above is a summary, other inclusion criteria details may apply.
Exclusion criteria
* 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. * 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. * Isolated Extramedullary (EM) Disease. * For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts. * Current autoimmune disease or history of autoimmune disease with potential CNS involvement. * Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication. * 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. * Testicular leukemia. * History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy. * Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy. * Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions). * Immunotherapy within 4 weeks before start of protocol-specified therapy. * 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. * Currently receiving treatment in or less than 30 days or 5 half-lives since ending treatment on another investigational study(ies). * Abnormal screening laboratory parameters. * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs) | Up to 29 days |
| Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs) | Up to approximately 28 weeks |
| Dose Escalation Phase: Number of participants who experience one or more serious TEAEs | Up to approximately 28 weeks |
| Dose Escalation Phase: Number of participants who experience one or more treatment-related TEAEs | Up to approximately 28 weeks |
| Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs) of Interest (AEIs) | Up to approximately 28 weeks |
| Dose Expansion and Phase 2 Ph-IIR cohort: Number of participants who achieve complete remission (CR) / complete remission with partial hematological recovery (CRh) | Up to 10 weeks |
| Phase 2 Ph-IIC cohort: Maximum concentration (Cmax) of blinatumomab SC1 and SC2 | Up to approximately 4 weeks |
| Phase 2 Ph-IIC cohort: Average concentration (Cavg) of blinatumomab SC1 and SC2 | Up to approximately 4 weeks |
| Phase 2 Ph-IIC cohort: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2 | Up to approximately 4 weeks |
| Phase 2 Ph-IIC cohort: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2 | Up to approximately 4 weeks |
| Phase 2 Ph-IIM cohort: Number of participants who achieve CR with MRD-negative response | Up to 10 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation and Dose Expansion Phase: Minimum concentration over the dosing interval (Cmin) of blinatumomab | Up to approximately 10 weeks | — |
| Dose Escalation and Dose Expansion Phase: Cmax of blinatumomab | Up to approximately 10 weeks | — |
| Dose Escalation and Dose Expansion Phase: Tmax of blinatumomab | Up to approximately 10 weeks | — |
| Dose Escalation and Dose Expansion Phase: AUC of blinatumomab | Up to approximately 10 weeks | — |
| Dose Escalation Phase and Phase 2 (Ph-IIC cohort): Number of participants who achieve CR/CRh | Up to 10 weeks | — |
| 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 | Up to approximately 28 weeks | — |
| Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Overall survival (OS) | Up to approximately 2 years | — |
| Dose Expansion Phase and Phase 2 (Ph-IIR cohort and Ph-IIC cohort): Duration of response | Up to approximately 2 years | — |
| Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Relapse free survival | Up to approximately 2 years | — |
| 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 | Up to approximately 28 weeks | — |
| 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 | Up to approximately 2 years | — |
| 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 | Up to approximately 28 weeks | — |
| Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more AEIs | Up to approximately 28 weeks | — |
| Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Summary scores of quality of life at each assessment as assessed by the EORTC QLQ-C30 for participants aged ≥ 17 years at the time of consent | Baseline (Day 1) up to approximately 28 weeks | The EORTC QLQ-C30 is defined as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. |
| Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Change from baseline of quality of life as assessed by the EORTC QLQ-C30 for participants aged ≥ 17 years at the time of consent | Baseline (Day 1) up to approximately 28 weeks | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Summary scores of quality of life at each assessment as assessed by PedsQL Generic Core Scale for participants aged 12 to < 17 years at time of consent | Baseline (Day 1) up to approximately 28 weeks | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Change from baseline of quality of life as assessed by PedsQL Generic Core Scale for participants aged 12 to < 17 years at time of consent | Baseline (Day 1) up to approximately 28 weeks | — |
| Phase 2 (Ph-IIR cohort): Number of participants who achieve CR | Up to 10 weeks | — |
| Phase 2 (Ph-IIR cohort): Number of participants who achieve CR, CRh, CRi (complete remission with incomplete hematological recovery) or blast free hypoplastic or aplastic bone marrow (BM) | Up to 10 weeks | — |
| Phase 2 (Ph-IIM cohort): Number of participants who achieve CR, CRh, CRi or blast free hypoplastic or aplastic BM with MRD-negative response | Up to 10 weeks | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Number of participants who achieve CR or CRh with MRD-negative response | Up to 10 weeks | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Duration of molecular response | Up to approximately 2 years | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Cmax of blinatumomab for participants participating in intense PK sampling assessment | Up to approximately 4 weeks | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Tmax of blinatumomab for participants participating in intense PK sampling assessment | Up to approximately 4 weeks | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): AUC of blinatumomab for participants participating in intense PK sampling assessment | Up to approximately 4 weeks | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Blinatumomab serum concentrations for participants not participating in intense PK sampling assessment | Up to approximately 4 weeks | — |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Proportion of time on treatment with high side effect bother from baseline to end of treatment as measured by Functional Assessment of Chronic Illness Therapy (FACIT) GP5 item for participants aged ≥ 17 years | Baseline (Day 1) up to approximately 28 weeks | This endpoint applies to participants aged ≥ 17 years at time of consent. |
| Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Pain difference between pain score before and after injection as reported using the Numeric Rating Scale (NRS-11) for participants aged 12 to < 17 years at time of consent | Up to approximately 28 weeks | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, Israel, Italy, Japan, Mexico, Netherlands, Romania, South Korea, Spain, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORMD
Amgen
Outcome results
None listed