Belinostat in Combination With Azacitidine or Pralatrexate for the Treatment of Relapse or Refractory T-cell Lymphoma

Summary

This phase I trial tests the safety, side effects and best dose of azacitidine in combination with belinostat and how well the combination works in treating patients with follicular helper T cell lymphoma (TFH) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). This phase I trial also tests the safety, side effects and best dose of pralatrexate in combination with belinostat and how well the combination works in treating patients with relapsed or refractory peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL) with large cell transformation and cytotoxic phenotype. Azacitidine stops cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. It is a type of antimetabolite. Pralatrexate stops cells from using folic acid to make DNA. This may help keep cancer cells from growing and may kill them. Pralatrexate is a type of antimetabolite and a type of dihydrofolate reductase inhibitor. Belinostat blocks certain enzymes needed for cell division and may kill cancer cells. 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. It is a type of histone deacetylase inhibitor, a type of antiangiogenesis agent, and a type of chemosensitizer. Giving azacitidine in combination with belinostat may be safe, tolerable, and/or effective in treating patients with relapsed/refractory (R/R) TFH. In additional, giving pralatrexate in combination with belinostat may be safe, tolerable, and/or effective in treating patients with R/R PTCL and CTCL with large cell transformation and cytotoxic phenotype.

Conditions

• Recurrent Anaplastic Large Cell Lymphoma
• Recurrent Enteropathy-Associated T-Cell Lymphoma
• Recurrent Follicular Helper T-Cell Lymphoma
• Recurrent Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type
• Recurrent Follicular Helper T-Cell Lymphoma, Follicular-Type
• Recurrent Follicular Helper T-Cell Lymphoma, Not Otherwise Specified
• Recurrent Hepatosplenic T-Cell Lymphoma
• Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
• Recurrent Monomorphic Epitheliotropic Intestinal T-cell Lymphoma
• Recurrent Peripheral T-Cell Lymphoma, Not Otherwise Specified
• Recurrent Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma
• Recurrent Primary Cutaneous Gamma-Delta T-Cell Lymphoma
• Recurrent Subcutaneous Panniculitis-Like T-Cell Lymphoma
• Refractory Anaplastic Large Cell Lymphoma
• Refractory Enteropathy-Associated T-Cell Lymphoma
• Refractory Follicular Helper T-Cell Lymphoma
• Refractory Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type
• Refractory Follicular Helper T-Cell Lymphoma, Follicular-Type
• Refractory Follicular Helper T-Cell Lymphoma, Not Otherwise Specified
• Refractory Hepatosplenic T-Cell Lymphoma
• Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
• Refractory Monomorphic Epitheliotropic Intestinal T-cell Lymphoma
• Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified
• Refractory Primary Cutaneous CD8-Positive Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma
• Refractory Primary Cutaneous Gamma-Delta T-Cell Lymphoma
• Refractory Subcutaneous Panniculitis-Like T-Cell Lymphoma

Interventions

DRUG

Azacitidine

Given SC

DRUG

Belinostat

Given IV

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

PROCEDURE

FDG-Positron Emission Tomography

Undergo FDG-PET

OTHER

Fludeoxyglucose F-18

Given FDG

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

DRUG

Pralatrexate

Given SC

OTHER

Questionnaire Administration

Ancillary studies

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Christina Poh · City of Hope Medical Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-01-03

Primary Completion

2029-11-24

Completion

2029-11-24

FDA Drug

Yes

Countries

• United States

Study Locations