AML, Adult, MDS
Conditions
Brief summary
This is a Phase 1b open-label, multicenter, dose-escalation and dose-optimization study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor efficacy of eganelisib as monotherapy and in combination with cytarabine in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML) or r/r higher-risk myelodysplastic syndromes (HR-MDS). The study consists of 2 parts: * Part 1: Dose Escalation (DE) in both monotherapy and in combination. * Part 2: Dose Optimization
Interventions
DRUGEganelisib
eganelisib will be administered as monotherapy
DRUGEganelisib in combination with cytarabine
eganelisib will be administered in combination with cytarabine
Sponsors
Stelexis BioSciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathological diagnosis of either: AML according to World Health Organization (WHO) 2022 revised criteria per the local pathology report and with ≥10% bone marrow blasts (acute promyelocytic leukemia is excluded but secondary AML and treatment-related AML can be included); Higher-risk (IPSS-R Intermediate, High or Very High Risk at time of study entry) myelodysplastic syndromes (HR-MDS) according to WHO 2022 revised criteria per the local pathology report and with ≥10% bone marrow blasts. * Eastern Cooperative Oncology Group (ECOG) performance status ≤2. * Adequate hepatic and renal function measured within 7 days prior to the first dose of eganelisib.
Exclusion criteria
* Autologous or allogeneic stem cell transplant within 6 months prior to Cycle 1 Day 1. * Receiving immunosuppressants (eg, cyclosporin) or systemic steroids (except for steroid use as cortisol replacement therapy in documented adrenal insufficiency). * Active fungal disease or uncontrolled infection of any kind; patients receiving antibiotic, antifungal or antiviral treatment must be afebrile and hemodynamically stable for \>72 hours prior to treatment * WBC count \>25 × 10\^9/L measured within 7 days prior to the first dose of eganelisib (hydroxyurea is permitted to decrease the WBC count). * Presence of a clinically significant non-hematologic toxicity of prior therapy that has not resolved to Grade ≤1 or Baseline, whichever is worst, as determined by NCI CTCAE v 5.0, except alopecia or skin pigmentation. Fatigue and neuropathy must have resolved to Grade ≤2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 | 12 months |
| Incidence and severity of dose-limiting toxicities (DLTs) in DLT evaluable patients during Cycle 1 | 28-35 days |
| Preliminary clinical activity as evaluated per European LeukemiaNet (ELN) 2022 criteria for AML and International Working Group (IWG) 2023 criteria for HR-MDS | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration time curve extrapolated to the last measurable time point [AUClast] of eganelisib and cytarabine | 112 days |
| Maximum concentration [Cmax] of eganelisib and cytarabine | 112 days |
| Time of maximum concentration [Tmax] of eganelisib and cytarabine | 112 days |
| Plasma half-life [t1/2] of eganelisib and cytarabine | 112 days |
| Measure plasma concentrations of eganelisib and determine model-based PK parameters | 112 days |
Countries
Spain, United States
Contacts
CONTACTClinical Trials Office Stelexis
Outcome results
None listed