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

NCT07691450 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 25715NCI-2026-04270P30CA033572
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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, Angioimmunoblastic-Type; Recurrent Follicular Helper T-Cell Lymphoma, Not Otherwise Specified; Recurrent Hepatosplenic T-Cell 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; Refractory Anaplastic Large 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 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; Recurrent Follicular Helper T-Cell Lymphoma; Recurrent Follicular Helper T-Cell Lymphoma, Follicular-Type; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous Gamma-Delta T-Cell Lymphoma; Refractory Enteropathy-Associated T-Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Monomorphic Epitheliotropic Intestinal T-cell Lymphoma; Recurrent Subcutaneous Panniculitis-Like T-Cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• Occurrence of dose-limiting toxicities (DLT) (Arm A)

  Observed toxicities will be summarized by type, severity, timing of onset, and attribution, and will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 6.0.

  Prior to cycle 2 day 1 (cycle length = 28 days)

• Occurrence of DLT (Arm B)

  Observed toxicities will be summarized by type, severity, timing of onset, and attribution, and will be graded according to the CTCAE, version 6.0.

  Prior to cycle 2 day 1 (cycle length = 21 days)

• Maximum tolerated dose (MTD) (Arm A)

  Will be defined as the highest dose of azacitidine tested in which at most 1 out of 6 DLT-evaluable patients treated at that dose experience a DLT. The MTD will be designated as the recommended phase 2 dose (RP2D), provided no additional safety concerns are identified.

  During the first cycle of treatment (cycle length = 28 days)

• MTD (Arm B)

  Will be defined as the highest dose of pralatexate tested in which at most 1 out of 6 DLT-evaluable patients treated at that dose experience a DLT. The MTD will be designated as the RP2D, provided no additional safety concerns are identified.

  During the first cycle of treatment (cycle length = 21 days)

Secondary Outcomes (10)

• Overall response rate (ORR) (Arm A)

  Up to 5 years

• ORR (Arm B)

  Up to 5 years

• Complete response (CR) rate (Arm A)

  Up to 5 years

• CR rate (Arm B)

  Up to 5 years

• Time to next treatment (TTNT) (Arm A)

  From the first dose of study treatment to initiation of subsequent anti-lymphoma therapy, assessed up to 5 years

Study Arms (2)

Arm A (azacitidine, belinostat)

EXPERIMENTAL

Patients receive azacitidine SC on days 1-5 and belinostat IV over 30-45 minutes on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and FDG-PET, and CT or PET/CT throughout the study.

Drug: Azacitidine; Drug: Belinostat; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: FDG-Positron Emission Tomography; Other: Fludeoxyglucose F-18; Procedure: Positron Emission Tomography; Other: Questionnaire Administration

Arm B (pralatrexate, belinostat)

EXPERIMENTAL

Patients receive pralatrexate SC on days 8 and 15 and belinostat IV over 30-45 minutes on days 1-3 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and FDG-PET, and CT or PET/CT throughout the study.

Drug: Belinostat; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: FDG-Positron Emission Tomography; Other: Fludeoxyglucose F-18; Procedure: Positron Emission Tomography; Drug: Pralatrexate; Other: Questionnaire Administration

Interventions

Azacitidine DRUG

Given SC

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Arm A (azacitidine, belinostat)

Belinostat DRUG

Given IV

Also known as: Beleodaq, PXD 101, PXD-101, PXD101

Arm A (azacitidine, belinostat); Arm B (pralatrexate, belinostat)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm A (azacitidine, belinostat); Arm B (pralatrexate, belinostat)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (azacitidine, belinostat); Arm B (pralatrexate, belinostat)

FDG-Positron Emission Tomography PROCEDURE

Undergo FDG-PET

Also known as: FDG, FDG-PET, FDG-PET Imaging

Arm A (azacitidine, belinostat); Arm B (pralatrexate, belinostat)

Fludeoxyglucose F-18 OTHER

Given FDG

Also known as: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Arm A (azacitidine, belinostat); Arm B (pralatrexate, belinostat)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm A (azacitidine, belinostat); Arm B (pralatrexate, belinostat)

Pralatrexate DRUG

Given SC

Also known as: 10-propargyl-10-deazaaminopterin, Difolta, Folotyn, PDX

Arm B (pralatrexate, belinostat)

Questionnaire Administration OTHER

Ancillary studies

Arm A (azacitidine, belinostat); Arm B (pralatrexate, belinostat)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Enteropathy-Associated T-Cell Lymphoma; Lymphoma, T-Cell; Subcutaneous panniculitis-like T-cell lymphoma

Interventions

Azacitidine; belinostat; Specimen Handling; Fluorodeoxyglucose F18; Magnetic Resonance Spectroscopy; 10-propargyl-10-deazaaminopterin

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Deoxyglucose; Deoxy Sugars; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Christina Poh

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2026
• First Posted: July 9, 2026
• Study Start (Estimated): January 3, 2027
• Primary Completion (Estimated): November 24, 2029
• Study Completion (Estimated): November 24, 2029
• Last Updated: July 9, 2026

Record last verified: 2026-07

Locations

US (1)