NCT06399640

Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

Phase Ib Study of Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of eltanexor in combination with venetoclax for the treatment of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Eltanexor works by trapping "tumor suppressing proteins" within the cell, thus causing the cancer cells to die or stop growing. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving eltanexor together with venetoclax may be safe, tolerable and/or effective in treating patients with relapsed or refractory MDS or AML.

Detailed description

Primary objective: • To establish the safe and biologically effective dose (BED) of eltanexor in combination with venetoclax in patients with R/R MDS and/or AML Secondary objectives: * To estimate the complete remission (CR) rate with eltanexor and venetoclax in patients with R/R MDS and/or AML * To assess the overall response rate (ORR) following treatment with eltanexor/venetoclax * To assess the overall survival of patients * To assess the progression free survival (PFS) and duration of response (DOR) in patients treated with eltanexor/venetoclax Exploratory objectives: * To assess differential response between MDS and AML cohorts * To develop and evaluate a phenotypic flow-based assay to predict response to eltanexor/venetoclax * To assess the effect of mutational changes on response to eltanexor/venetoclax * To measure the rates of measurable residual disease with eltanexor/venetoclax OUTLINE: This is a dose-escalation study of eltanexor in combination with venetoclax. Patients receive eltanexor orally (PO) once per day (QD) for 5 days per week for 14, 21, or 28 days every cycle, and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for up to 24 months.

Conditions

• Relapsed Myelodysplastic Syndrome
• Refractory Myelodysplastic Syndrome
• Acute Myeloid Leukemia
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Eltanexor	Eltanexor will be taken by mouth
DRUG	Venetoclax	Venetoclax will be taken by mouth
PROCEDURE	Bone Marrow Aspiration and Biopsy	Undergo bone marrow aspiration and biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection

Timeline

• Start date: 2024-08-14
• Primary completion: 2027-02-01
• Completion: 2027-10-01
• First posted: 2024-05-06
• Last updated: 2025-03-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study