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

Starting soon · Phase 1

Conditions studied: 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

In brief

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.

Key facts

Study ID: NCT07691450
Run by: City of Hope Medical Center
People needed: 40
Starts: 2027-01-03
Expected to finish: 2029-11-24
Last updated by the study team: 2026-07-09

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Ability to understand and willingness to sign a written informed consent document
Documented informed consent of the participant and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines
Age: ≥ 18 years
Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) Scale (performance status [PS]) at time of enrollment. Patients with a performance status of 2 on the ECOG Scale due to lymphoma may be eligible with principal investigator (PI) approval
Histologically confirmed PTCL in the following subtypes below (by local review). Eligible histologies include:
Arm A
Histologically confirmed TFH cell lymphomas. Nodal TFH cell lymphomas encompasses three subtypes:
Angioimmunoblastic T-cell lymphoma (AITL)(World Health Organization [WHO]4R)/follicular helper T-cell lymphoma (TFH lymphoma), angioimmunoblastic type (ICC)/nodal TFH cell lymphoma, angioimmunoblastic-type (WHO5)
Nodal PTCL with TFH phenotype (nodal PTCL, TFH)(WHO4R)/TFH lymphoma, NOS (ICC)/nodal TFH cell lymphoma, not otherwise specified (NOS) (WHO5)
Follicular T-cell lymphoma (FTCL)(WHO4R)/TFH lymphoma, follicular type (ICC)/ nodal TFH cell lymphoma, follicular-type (WHO5)
Arm B
Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS)
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)
Enteropathy-associated T-cell lymphoma (EATL)
Anaplastic large cell lymphoma (ALCL)
Hepatosplenic T-cell lymphoma
Cutaneous T-cell lymphoma (CTCL) with large cell transformation
Subcutaneous panniculitis-like T-cell lymphoma
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL)
Primary cutaneous gamma-delta T-cell lymphoma (PCGDTL)
Must have received at least one prior systemic therapy and have an indication for treatment
NOTE: For systemic ALCL, prior systemic therapy must have included brentuximab vedotin
Measurable disease, including at least 1 nodal site measuring ≥ 1.5cm or 1 extranodal site measuring 1.0 cm in longest dimension on CT or FDG-PET or marrow-only disease (disease only found on bone marrow biopsy)
Life expectancy > 12 weeks
Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3

You may not qualify if…

Patients who received prior therapy with belinostat or azacitidine (Arm A) or belinostat or pralatrexate (Arm B) without having had evidence of objective response (i.e. patients whose best response was stable disease or progressive disease)
Note: Patients who previously responded to any of these agents are eligible. Their last dose of either belinostat, azacitidine or pralatrexate must be > 14 days prior to day 1 of protocol therapy
Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days or five half-lives (whichever is shorter for non-radiation therapy) prior to day 1 of protocol therapy
Prior autologous stem cell transplantation within 60 days of day 1 of protocol therapy
Major surgery within 4 weeks prior to the start of cycle 1, other than for diagnosis confirmation
UGT1A1 inhibitors within 14 days prior to day 1 of protocol therapy
History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) which requires systemic treatment. Patients may proceed with screening during treatment for infection, but systemic treatment must be completed by cycle 1 day 1
If a patient has signs/symptoms suggestive of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the patient must have a negative molecular (e.g., polymerase chain reaction [PCR]) test or 2 negative antigen test results at least 24 hours apart. Patients who do not meet SARS-CoV-2 infection eligibility criteria must be screen-failed and may only be re-screened if the following have been met:
At least 10 days since first positive test result have passed in asymptomatic patients or at least 10 days since recovery, defined as resolution of fever without use of antipyretics and improvement in symptoms
Subjects with concurrent active hepatitis B (defined as hepatitis B virus surface antigen [HBsAg] positive and/or detectable hepatitis B virus [HBV] DNA) and/or hepatitis C virus (defined as anti-hepatitis C virus [HCV] antibody [Ab] positive and detectable HCV ribonucleic acid [RNA]) infection.
Hepatitis B and C screening tests are not required unless: (1) Known history of HBV and HCV infection or (2) As mandated by local health authority
Subjects with HIV infection
Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Note: If such malignancies were treated with either belinostat, azacitidine, or pralatrexate the 14 day washout applies
Females only: Pregnant or breastfeeding
Known active central nervous system lymphoma
Participants who are receiving other investigational agents
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Where it is running

City of Hope Medical Center — Duarte, California, United States

Full record on ClinicalTrials.gov

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