NCT03955783

Venetoclax and Selinexor in Treating Patients with Relapsed or Refractory High Risk Hematologic Malignancies

An Investigator-Sponsored Phase Ib Trial of Venetoclax and SINE: Selective Inhibition of Nuclear Export in Patients with High Risk Hematologic Malignancies

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 78 (actual)
• Sponsor: Sanjay Mohan · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the toxicity and dosing of venetoclax in combination with selinexor, and how well the combination works in treatment of patients with high risk hematologic malignancies such as diffuse large B-cell lymphoma and acute myeloid leukemia that has come back (recurrent) or does not respond to initial treatment (refractory). Venetoclax functions by inhibiting a protein in the body called bcl-2, which is involved in slowing down the normal process by which old cells in the body are cleared (called apoptosis). Selinexor functions by trapping "tumor suppressing proteins" within the cell and causing the cancer cells to die or stop growing. This study examines the effects, if any, of selinexor and venetoclax on high risk hematologic malignancies and on the body, including any side-effects.

Detailed description

Primary: * Escalation: Identify the maximum tolerated dose(s) (MTD) and recommended phase 2 dose(s) (RP2D) of SEL-VEN combination therapy in patients with diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukemia (AML). * Expansion: Determine the overall response rate of SEL-VEN combination therapy in patients with relapsed/refractory hematologic malignancies. Exploratory Objectives: * To explore biomarkers of response to SEL-VEN therapy. * To determine the progression free survival (PFS) and overall survival (OS) of SEL-VEN combination therapy. OUTLINE: This is a dose-escalation study. Patients receive venetoclax orally (PO) once daily (QD) on days 1-28. Patients with DLBCL receive selinexor PO on days 1, 8, 15, and 22 of each cycle. Patients with venetoclax-naive AML are treated with selinexor on days 8, 15, and 22 of cycle 1, followed by days 1, 8, 15, and 22 of subsequent cycles. Venetoclax-refractory AML patients begin both drugs on cycle 1 day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 28 days and every 3 months for 2 years.

Conditions

• Diffuse Large B-cell Lymphoma
• Acute Myeloid Leukemia
• Non-Hodgkin's Lymphoma

Interventions

Type	Name	Description
DRUG	Venetoclax	Given by mouth
DRUG	Selinexor	Given by mouth

Timeline

• Start date: 2019-06-21
• Primary completion: 2024-09-01
• Completion: 2024-09-01
• First posted: 2019-05-20
• Last updated: 2024-10-26

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study