Trials / Active Not Recruiting

Active Not RecruitingNCT05627245

Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment

Phase 1/Expansion Study of Tazemetostat Plus Belinostat for the Treatment of Relapsed or Refractory Lymphoma

Status: Active Not Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 48 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of combination therapy with tazemetostat and belinostat in treating patients with lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Tazemetostat is in a class of medications called EZH2 inhibitors. The EZH2 gene provides instructions for making a type of enzyme called histone methyltransferase which is involved in gene expression and cell division. Blocking EZH2 may help keep cancer cells from growing. Belinostat is in a class of medications called histone deacetylase inhibitors. Histone deacetylases are enzymes needed for cell division. Belinostat may kill cancer cells by blocking histone deacetylase. It may also prevent the growth of new blood vessels that tumors need to grow and may help make cancer cells easier to kill with other anticancer drugs. There is some evidence in animals and in living human cells that combination therapy with tazemetostat and belinostat can shrink or stabilize cancer, but it is not known whether this will happen in people. This trial may help doctors learn more about treatment of patients with relapsed or refractory lymphoma.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of tazemetostat and belinostat in combination in patients with relapsed or refractory lymphoma. (Phase I: Dose escalation) II. Evaluate the safety and toxicity of the combination tazemetostat and belinostat. (Phase I: Dose escalation) III. Assess the safety and tolerability of tazemetostat and belinostat in patients with germinal-center derived B-cell lymphoma (follicular lymphoma, transformed disease, diffuse large B-cell lymphoma germinal center B-cell type \[GC-DLBCL\] defined by Hans criteria), and T-cell lymphomas. (Phase I: Dose expansion) IV. Assess the impact of EZH2, CREBBP, and EP300 mutations on response to dual epigenetic targeting. (Phase I: Dose expansion) SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the pharmacokinetic profile for tazemetostat and belinostat when given as a combination. III. Define the overall response rate (ORR), progression free survival (PFS), and duration of response (DOR) in patients with relapsed or refractory EZH2 mutated and EZH2 wild-type germinal-center derived B-cell lymphoma (follicular lymphoma, transformed disease, GC-DLBCL defined by Hans criteria), as well as T-cell lymphomas. IV. To describe the maximum number of cycles received, the number of dose reductions and delays at the MTD. EXPLORATORY OBJECTIVES: I. Determine a biomarker for response by assessing the basal mutation and gene expression status of key epigenetic regulators and correlating this signature with the response to the combination. II. Determine the change in gene expression in tumor tissue following exposure the combined epigenetic therapy. III. Determine the effect of combination epigenetic therapy on modulation of acetylation and methylation of histone K27. IV. Determine the effect of combination epigenetic therapy on modulation of the immune response. OUTLINE: This is a phase I dose-escalation study of tazemetostat and belinostat followed by a dose-expansion study. Patients receive tazemetostat orally (PO) twice daily (BID) on days 2-21 of cycle 1 and days 1-21 of subsequent cycles, and belinostat intravenously (IV) over 30-180 minutes on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo a tumor biopsy during screening and on study (dose-expansion only). Patients undergo blood sample collection while on study and computed tomography (CT) or positron emission tomography (PET)/CT scan throughout the study. After completion of study treatment, patients are followed up at 4 weeks, then every 3 months for a year or until they begin a new treatment for their disease.

Conditions

Interventions

Type	Name	Description
DRUG	Belinostat	Given IV
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT scan
OTHER	Pharmacokinetic Study	Pharmacokinetic study
PROCEDURE	Positron Emission Tomography and Computed Tomography Scan	Undergo PET-CT
DRUG	Tazemetostat	Given PO

Timeline

Start date: 2023-03-01
Primary completion: 2026-09-01
Completion: 2026-09-01
First posted: 2022-11-25
Last updated: 2026-04-13

Locations

11 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05627245. Inclusion in this directory is not an endorsement.