Ignite Creation Date:
2024-05-06 @ 6:20 PM
Last Modification Date:
2024-10-26 @ 2:46 PM
Study NCT ID:
NCT05627245
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2022-11-23
Brief Title:
Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase 1Expansion Study of Tazemetostat Plus Belinostat for the Treatment of Relapsed or Refractory Lymphoma
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial tests the safety side effects and best dose of combination therapy with tazemetostat and belinostat in treating patients with lymphomas that have returned relapsed or resisted 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 aggressive B-cell lymphoma transformed disease diffuse large B-cell lymphoma germinal center B-cell type GC-DLBCL defined by Hans criteria 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 aggressive germinal-center derived B-cell lymphoma transformed disease GC-DLBCL defined by Hans criteria
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 positron emission tomographycomputed tomographyPETCT scan throughout the study Patients may also undergo computed tomography CT scan alone 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
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 aggressive B-cell lymphoma transformed disease diffuse large B-cell lymphoma germinal center B-cell type GC-DLBCL defined by Hans criteria 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 aggressive germinal-center derived B-cell lymphoma transformed disease GC-DLBCL defined by Hans criteria
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 positron emission tomographycomputed tomographyPETCT scan throughout the study Patients may also undergo computed tomography CT scan alone 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2022-05327 | REGISTRY | None | None |
| 10500 | OTHER | None | None |
| 10500 | OTHER | None | None |
| UM1CA186689 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA186689 |