Clinical trial NCT06533761: Eganelisib as Monotherapy and in Combination With Cytarabine in Relapsed/Refractory AML
Official title: A Phase 1b Open-Label Study to Evaluate the Safety and Tolerability of Eganelisib as Monotherapy and in Combination With Cytarabine in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: AML, Adult
MDS
Lead sponsor: Stelexis BioSciences
Sponsor class: INDUSTRY
First posted: 2024-08-01
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 12 months
measure: Incidence and severity of dose-limiting toxicities (DLTs) in DLT evaluable patients during Cycle 1
timeFrame: 28-35 days
measure: Preliminary clinical activity as evaluated per European LeukemiaNet (ELN) 2022 criteria for AML and International Working Group (IWG) 2023 criteria for HR-MDS
timeFrame: 12 months
Secondary outcomes:
measure: Area under the plasma concentration time curve extrapolated to the last measurable time point [AUClast] of eganelisib and cytarabine
timeFrame: 112 days
measure: Maximum concentration [Cmax] of eganelisib and cytarabine
timeFrame: 112 days
measure: Time of maximum concentration [Tmax] of eganelisib and cytarabine
timeFrame: 112 days
measure: Plasma half-life [t1/2] of eganelisib and cytarabine
timeFrame: 112 days
measure: Measure plasma concentrations of eganelisib and determine model-based PK parameters
timeFrame: 112 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: NYC
country: United States
facility: Montefiore Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
state: Caceres
Study officials:
affiliation: Stelexis BioSciences
name: Mieke Ptaszynski, MD
role: STUDY_DIRECTOR
References: