Recruiting

Phase 1

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

Sponsor:

City of Hope Medical Center

Code:

NCT07691450

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

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Azacitidine

Belinostat

Biospecimen Collection

Computed Tomography

FDG-Positron Emission Tomography

Study Details

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

Recurrent Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type

Recurrent Follicular Helper T-Cell Lymphoma, Follicular-Type

Study ID

NCT07691450

Start date

Jan 3, 2027

Status verified date

Oct, 2026

Completion date

Nov 24, 2029

Anticipated

Primary completion date

Nov 24, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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

NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
With bone marrow involvement: ANC ≥ 750/mm\^3

NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
Without bone marrow involvement: Platelets ≥ 75,000/mm\^3

NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
With bone marrow involvement: Platelets ≥ 50,000/mm\^3

NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
Hemoglobin ≥ 8g/dL

NOTE: Red blood cell transfusions are not permitted within 7 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

NOTE: Patients with documented Gilbert's disease, documented liver or pancreatic involvement in lymphoma may be enrolled if total bilirubin ≤ 3.0 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN
Aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5 x ULN for patients with liver involvement by lymphoma
Alanine aminotransferase (ALT) ≤ 3.0 x ULN OR ≤ 5 x ULN for patients with liver involvement by lymphoma
Measured or calculated creatinine clearance ≥ 60 mL/min (glomerular filtration rate \[GFR\] can also be used in place of creatinine clearance \[CrCl\])
If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN
If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test

If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual intercourse for the course of the study and after completion of study treatment as described below separately for males and females

WOCBP must remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of ≤ 1% per year during the treatment period and for at least 1 month after the last dose of study treatment. Women must refrain from donating eggs during this same period

Examples of contraceptive methods with a failure rate of ≤ 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception
For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:

With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 1 month after the last treatment. Men must refrain from donating sperm during this same period
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of preventing drug exposure
Childbearing potential defined as being post-menarcheal (women only), not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) within 7 days prior to cycle 1 day 1, for indications other than lymphoma symptom control. Patients who require lymphoma symptom control during screening may receive steroids in the following manner:

Up to 30 mg/day of prednisone or equivalent may be used for lymphoma symptom control during screening, including prior to finalization of staging (not included as part of pre-phase treatment). If glucocorticoid treatment is urgently required at higher doses for lymphoma symptom control prior to the start of study treatment, tumor assessments must be completed prior to initiation of > 30-100 mg/day of prednisone or equivalent. Prednisone > 30-100 mg/day or equivalent may be given for a maximum of 7 days as a pre-phase treatment. If patients exceed the allowed dosing of corticosteroids, patients may still be eligible for the study provided that baseline imaging is performed (or repeated) after completion of the course of higher dose of steroids. Allowed corticosteroid dosing resets from the point of imaging forward and patients who do not exceed the allowed corticosteroid dosing from the point of imaging until initiation of study treatment may enroll. Steroids at a dose less than the equivalent of 10 mg/day of prednisone and inhaled, nasal, and topical steroids are permitted. Adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease are permitted. Treatment with a short course of steroids (< 7 days) up to 7 days prior to cycle 1 day 1 is permitted

Exclusion Criteria:

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)

Study Design

Enrollment

40 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (azacitidine, belinostat)

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.

experimental: Arm B (pralatrexate, belinostat)

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.

Interventions

Azacitidine

Given SC

Belinostat

Given IV

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT or PET/CT

FDG-Positron Emission Tomography

Undergo FDG-PET

Fludeoxyglucose F-18

Given FDG

Positron Emission Tomography

Undergo PET/CT

Pralatrexate

Given SC

Questionnaire Administration

Ancillary studies

Primary outcome measure

Occurrence of dose-limiting toxicities (DLT) (Arm A) [ Time Frame: Prior to cycle 2 day 1 (cycle length = 28 days) ]
Occurrence of DLT (Arm B) [ Time Frame: Prior to cycle 2 day 1 (cycle length = 21 days) ]
Maximum tolerated dose (MTD) (Arm A) [ Time Frame: During the first cycle of treatment (cycle length = 28 days) ]
MTD (Arm B) [ Time Frame: During the first cycle of treatment (cycle length = 21 days) ]

Central Contacts and Locations

Locations

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Christina Poh

626-256-4673 cpoh@coh.org

Principal Investigator:

Christina Poh

City of Hope at Georgia - Atlanta

Recruiting

Newnan, Georgia, United States, 30265

Contacts

Christina Poh, MD

770-400-6677 cpoh@coh.org

More Information

Sponsor

City of Hope Medical Center

Last update posted

Oct 30, 2026

Last verified

Oct, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-31. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-10-30. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.