Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, B-cell Acute Lymphoblastic Leukemia, Pediatric ALL, Pediatric ALL, B Cell, Pediatric ALL, Relapsed, Pediatric AML, Pediatric Cancer, Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, R/R AML, R/R B-cell ALL
Conditions
Keywords
R/R B-cell ALL, R/R AML, Pediatric AML, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Pediatric ALL, B Cell, Pediatric ALL, Pediatric ALL, Relapsed, Pediatric Cancer, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Sonrotoclax, Pediatric
Brief summary
The goal of this clinical trial is to learn if sonrotoclax (BGB-11417) is safe and may help treat children and adolescents with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) that has come back after treatment or has not responded to treatment. The study will also learn how the body processes sonrotoclax when it is given with other medicines. The main questions it aims to answer are: * Is sonrotoclax safe and well tolerated when given with other anti-cancer medicines? * How does the body absorb, process, and remove sonrotoclax? * Does treatment with sonrotoclax, in combination with other medicines, help reduce or eliminate leukemia? Researchers will give sonrotoclax together with other anti-cancer medicines to participants with relapsed or refractory AML or ALL. Participants will: * Take sonrotoclax in combination with other anti-cancer medicines * Have regular clinic visits for physical exams, blood tests, heart monitoring, and other safety assessments. * Provide blood samples to measure how the body processes sonrotoclax. * Have tests to evaluate how their leukemia responds to treatment. * Continue treatment as long as it is helping and side effects remain manageable, according to the study plan.
Interventions
DRUGsonrotoclax
Administered orally as a tablet
DRUGAzacitidine
administered intravenously or subcutaneously
DRUGInotuzumab ozogamicin
administered via intravenous infusion
DRUGDexamethasone
administered via intravenous injection or orally
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria Participants must meet all of the following criteria to be eligible for participation: 1. Have a performance status of Lansky ≥50 for participants ≤16 years of age or Karnofsky ≥50 for participants \>16 years of age. 2. Have adequate renal function, defined as an estimated or measured glomerular filtration rate (GFR) ≥60 mL/min. 3. Have adequate hepatic function, defined as: * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2.5 × the institutional upper limit of normal (ULN) * Total bilirubin ≤1.5 × the institutional ULN. 4. Have minimum cardiac function as defined in the study protocol. Acute Myeloid Leukemia (AML)-Specific Inclusion Criteria 1. Have a histologically confirmed diagnosis of acute myeloid leukemia (AML) that is relapsed or refractory (R/R) after ≥2 prior lines of systemic therapy. 2. Have ≥5% blasts in a bone marrow aspirate or biopsy sample, as assessed by morphology. Participants with extramedullary, non-central nervous system (CNS) disease are eligible. B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)-Specific Inclusion Criteria 1. Have a histologically confirmed diagnosis of B-cell precursor acute lymphoblastic leukemia (ALL) that is R/R after ≥2 prior lines of systemic therapy, including at least 1 line of blinatumomab-based therapy. 2. Have ≥5% blasts in a bone marrow aspirate or biopsy sample, as assessed by morphology. 3. Have leukemic blasts expressing cluster of differentiation 22 (CD22) on the cell surface, as assessed by flow cytometry of a bone marrow aspirate. Key
Exclusion criteria
Participants will be excluded from participation if any of the following apply: 1. Have central nervous system (CNS) 2 or CNS 3 disease at screening. 2. Have toxicity from prior anticancer therapy that has not recovered to ≤Grade 1, as defined by the applicable toxicity grading criteria. 3. Have a history of prior allogeneic stem cell transplantation \<90 days from enrollment or if if ≥ 90 days from enrollment, with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent. AML-Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Recommended Dose for Expansion (RDFE) of Sonrotoclax | From first dose through end of Cycle 1 (each cycle is 28 days); approximately 2 months | Dose selected based on safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity observed in Part 1, as determined by the Safety Monitoring Committee (SMC) |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose of study drug to 30 days after last dose; up to approximately 12 months in cohort 1 and 4 months in cohort 2. | Assessed by treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities,. Includes adverse events meeting protocol-defined dose-limiting toxicity (DLT) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration Measured Immediately Prior to the Next Scheduled Dose (Ctrough) for Sonrotoclax | Up to approximately 1 month | — |
| Area Under the Curve From Time Zero to Last Measurable Concentration (AUClast) for Sonrotoclax | Up to approximately 1 month | — |
| Complete Remission (CR) Rate | Up to approximately 2 months | Percentage of participants achieving a best overall response of complete remission (CR), as assessed by investigator's review |
| Time to Maximum Observed Plasma Concentration (Tmax) for Sonrotoclax | Up to approximately 1 month | — |
| Maximum Observed Plasma Concentration (Cmax) for Sonrotoclax | Up to approximately 1 month | — |
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed