Acute Myeloid Leukemia, AML, Adult
Conditions
Keywords
ALX148, CD47, SIRPalpha, azacitidine, venetoclax, evorpacept
Brief summary
This Phase 1/2 clinical study will evaluate evorpacept (ALX148) in combination with venetoclax and azacitidine for the treatment of patients with acute myeloid leukemia (AML).
Detailed description
The Phase 1 will consist of a dose escalation of evorpacept (ALX148) in combination with venetoclax and azacitidine to evaluate safety and tolerability, and to identify the recommended Phase 2 dose of evorpacept (ALX148) in combination with venetoclax and azacitidine. The Phase 2 will evaluate the efficacy of evorpacept (ALX148) in combination with venetoclax and azacitidine for patients with AML. While intended to be a Phase 1/2 clinical study, the study never moved forward to Phase 2.
Interventions
DRUGevorpacept
Fusion protein that blocks CD47-SIRPalpha pathway
DRUGvenetoclax
BCL-2 inhibitor
DRUGazacitidine
Hypomethylating agent (HMA)
Sponsors
ALX Oncology Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cytologically or histologically confirmed diagnosis of relapsed/refractory or newly diagnosed AML per WHO 2016 classification. * Phase 1a: AML that is relapsed/refractory or that is previously untreated in patients not considered suitable for intensive induction therapy. * Phase 1b: AML that is relapsed/refractory after prior treatment with a HMA-based regimen. * Phase 2: Previously untreated AML in patients who are not considered suitable candidates for intensive induction therapy. * Adequate renal and liver function. * Age ≥18 years. * Adequate performance status.
Exclusion criteria
* In Phase 1a and 1b, patients that have undergone prior allo-HSCT must be at least 3 months post-HSCT, without uncontrolled graft-versus-host disease (GVHD). For Phase 2, patients that have undergone prior allo-HSCT are excluded. * Patients with newly diagnosed AML with favorable risk cytogenetics such as t(8;21), inv(16), or t(16;16) as per the NCCN Guidelines Version 3, 2019 for AML. * Patients with acute promyelocytic leukemia (APL). * Prior treatment with any anti-CD47 or anti-SIRPalpha (signal regulatory protein alpha) agent. * Known active viral infections, including hepatitis B and C, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) related illness, or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Dose Limiting Toxicities (DLT) | Up to 28 days | Number of participants with a DLT |
| Phase 2: Composite complete remission rate (CRc) | Approximately 6 months | Number of participants achieving a complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) per European LeukemiaNet (ELN) 2017 criteria |
Countries
United States
Outcome results
None listed