Loading clinical trials...

Venetoclax and Selinexor in Treating Patients with Relapsed or Refractory High Risk Hematologic Malignancies | Clinical Trials | Clareo Health

COMPLETEDPHASE1

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

NCT03955783•Sanjay Mohan

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
•Age ≥ 18 years
•Life expectancy \> 12 weeks.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
•Histologically confirmed diagnosis of one of the following, in accordance with WHO diagnostic criteria:
•* Escalation:
•* Diffuse Large B-cell Lymphoma (DLBCL, including primary mediastinal large B cell lymphoma, T cell rich B cell lymphoma, and high-grade B cell lymphoma NOS). Patients with Burkitt's, lymphoblastic lymphoma, follicular lymphoma, and mantle cell lymphoma are not included. OR
•* Acute Myeloid Leukemia (AML)
•* Expansion:
•* Diffuse Large B-cell Lymphoma and acute myeloid leukemia as above.
+12 more criteria

Exclusion Criteria

•Patients who are pregnant or lactating
•Patients who received any systemic anticancer therapy including investigational agents or radiation ≤3 weeks (or ≤5 half-lives of the drug \[whichever is shorter\]) prior to C1D1. Hydroxyurea is permitted for up to 14 days in AML patients
•Inadequate recovery from toxicity attributed to prior anti-cancer therapy. With the exception of alopecia or fatigue, patients must have recovered to baseline or ≤ Grade 1 (NCI-CTCAE v4.03) residual toxicity prior to first dose of protocol-indicated treatment.
•Participation in another clinical trial with any investigational drug within 14 days prior to study enrollment.
•Patients included in the VEN refractory cohort that have discontinued venetoclax therapy (either monotherapy or combination) due to toxicity or hypersensitivity, including prior history of grade 3/4 TLS during prior VEN exposure
•In dose expansion cohorts, except venetoclax refractory cohort, no prior treatment with SINE compounds, another XPO1 inhibitor, or BCL-2 inhibitors.
•Active GVHD requiring calcineurin inhibitors or steroid dosing ≥ 10mg/day prednisone (or equivalent) or \< 3 months from allogenic hematopoietic cell transplant (HCT).
•Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral.
•Major surgery within 2 weeks of first dose of study drug.
•Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety.
+13 more criteria

Locations (4)

Roswell Park Cancer Center

Buffalo, New York, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Key Dates

Start Date

June 21, 2019

Primary Completion Date

September 1, 2024

Completion Date

September 1, 2024

Last Updated

October 26, 2024

Enrollment

ACTUAL participants

Conditions

Diffuse Large B-cell LymphomaAcute Myeloid LeukemiaNon-Hodgkin's Lymphoma

Interventions

Venetoclax

DRUG

Selinexor

DRUG

Phase I Study of HC-7366 for Acute Myeloid Leukemia

NCT06285890

Acute Myeloid Leukemia

View study

RECRUITINGPHASE2/PHASE3

A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

NCT05139017

DLBCLDiffuse Large B-Cell Lymphoma

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 26, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Phase I Study of HC-7366 for Acute Myeloid Leukemia

A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

VAC Regimen for AML Patients Who Failed to Response to VA Regimen

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Patients With Newly Diagnosed AML or MDS-EB-2

A Study of CBX-250 in Participants With Relapsed or Refractory Myeloid Leukemias