BY002 IIT Study in R/R Acute Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age16+
SponsorThe First Affiliated Hospital of Soochow University
About this trial
This is a single-center, open-label, investigator-initiated phase 1 study designed to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of the menin inhibitor BY002 in patients with relapsed or refractory acute leukemia. Eligible subjects include adult patients (≥18 years) with AML, ALL, or MPAL, excluding APL, who carry KMT2A rearrangement or NPM1 mutation and have no better treatment options.
The study will be conducted in a dose-escalation design (3+3) , followed by expansion at the recommended dose. BY002 is administered orally in 28-day cycles until disease progression, unacceptable toxicity, HSCT, withdrawal, or death.
The primary objectives are to determine the incidence of dose-limiting toxicities (DLTs) and serious adverse events (SAEs), and to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Secondary objectives include characterization of PK parameters, evaluation of safety (AEs, laboratory tests, vital signs, ECG), and assessment of efficacy endpoints such as complete remission (CR), composite remission (CRc), overall response rate (ORR), duration of response (DOR), event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), and cumulative incidence of relapse (CIR). Exploratory objectives include analysis of pharmacodynamic biomarkers (e.g., HOXA9, MEIS1, CD11b) and correlation of baseline genetic mutations (e.g., NPM1, KMT2A, FLT3, TP53, NUP98) with clinical outcomes.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥16 years.
Confirmed diagnosis of AML, ALL, or MPAL per WHO 2022 criteria.
Relapsed or refractory disease after ≥1 prior therapy.
Presence of KMT2A rearrangement or NPM1 mutation (preferred, but not exclusive).
Disqualifiers
Active central nervous system (CNS) leukemia. (Prior CNS involvement allowed if treated and controlled; CNS prophylaxis permitted.)
HBsAg positive must have negative HBV DNA.
HCV antibody positive must have negative HCV RNA.
Known HIV infection.
Trial design
Design model
Single group
Treatments tested in this trial
BY002
DrugBY002 capsule (oral) * Starting dose: 50 mg BID * Dose escalation: 100 mg BID → 150 mg BID → 200 mg BID (3+3 design) * Treatment cycle: 28 days, repeated until disease progression, unacceptable toxicity, HSCT, withdrawal, or death
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: BY002 treatmentExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of dose-limiting toxicities (DLT)
A DLT is defined as any ≥Grade 3 non-hematologic or ≥Grade 4 hematologic toxicity considered related to BY002, occurring during the DLT evaluation period. The number and proportion of participants with DLTs will be summarized.
Time frame
From Cycle 1 Day 1 (C1D1) through the end of the DLT observation period (Day 1-28; may extend to Day 42 if toxicity evaluation is delayed).2
Incidence of serious adverse events (SAEs)
SAEs will be defined and classified according to ICH E2A and CTCAE v5.0. The number and proportion of participants experiencing ≥1 SAE will be summarized.
Time frame
From Cycle 1 Day 1 (C1D1) until 30 days after the last dose.Secondary outcomes
1
Incidence, type, and severity of all adverse events (AEs)
AEs will be coded per MedDRA and graded by NCI CTCAE v5.0. Number, type, severity, and causality of AEs will be summarized.
Time frame
From first dose until 30 days after the last dose.2
Plasma concentrations of BY002 and its primary metabolite (M1)
PK parameters including Cmax, Tmax, AUC, t1/2, and CL/F will be calculated using non-compartmental analysis following single-dose and multiple-dose administration.
Time frame
Cycle 0 Day 1 (single-dose PK) and throughout treatment cycles, up to 30 days after the last dose.3
Proportion of participants achieving complete remission (CR/CRi) per ELN 2022 criteria
Response will be evaluated according to ELN 2022 criteria, including CR, CRi, PR, and MRD negativity rates.
Time frame
From first dose until disease progression, relapse, or death, assessed up to approximately 24 months.Other outcomes
1
Pharmacodynamic biomarker changes and correlation of baseline genomic mutations with clinical efficacy
Quantitative assessment of pharmacodynamic markers (e.g., HOXA9, MEIS1 expression) and exploratory analysis of association between baseline mutation profiles and treatment response or survival outcomes.
Time frame
From baseline until end of study (up to 24 months).Sponsors and contacts
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Source ClinicalTrials.gov