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PTCLPhase 2PTCLNCT04747236

Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator's Choice in PTCL

A Phase 2 study testing Azacytidine, Romidepsin and Belinostat in people with PTCL, run by University of Virginia at 6 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this study is to find out whether the combination treatment of romidepsin and oral azacytidine is safe and effective in patients with Peripheral T-Cell Lymphoma (PTCL). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
PTCL
What is being tested?
Azacytidine, Romidepsin and Belinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
6 sitesUnited States
Study dates
19 Feb 2021to 2 Jun 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible to participate in this study, an individual must meet all of the following criteria:
  • Patients must have histologically confirmed relapsed or refractory peripheral T-cell lymphoma as defined by 2016 WHO criteria (Section 13.7), who have progressed following one line of prior systemic therapy.
  • Patients are required to have no more than 3 lines of prior therapy (with cytoreductive therapy [ex ICE, DHAP, etc.] followed by autologous stem cell transplant counting as one line of therapy). Patients are eligible if they have relapsed after prior autologous or allogeneic stem cell transplant.
  • Patients with anaplastic large cell lymphoma are required to have received brentuximab vedotin (Bv) prior to study enrollment.
  • Measurable Disease as defined in Section 8.1.3.1.
  • Age ≥18 years.
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  • ECOG performance status ≤2
  • Patients must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count (ANC): ≥1000/mm3 (≥1000/dL); Platelets: > 75,000/mm3; Serum Creatinine:< 2 x ULN OR creatinine clearance >50 mL/min/for patients with creatinine levels above ULN; Bilirubin: ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4x ULN is allowed); AST and ALT: ≤ 2 x ULN OR ≤ 3 X ULN in presence of demonstrable liver involvement; Serum potassium: ≥ 3.8 mmol/L; Serum magnesium≥1.8 mg/dL.
  • Negative urine or serum pregnancy test for females of childbearing potential
  • All females of childbearing potential and male subjects must agree to use an effective method of contraception (see section 5.4 for more details)
  • Be willing and able to provide written consent or assent for the trial.

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • Diagnosis of patch/plaque stage mycosis fungoides
  • Prior Therapy: Prior exposure to any hypomethylating agent or any histone deacetylase inhibitor (ex: romidepsin, chidamide, belinostat, or vorinostat); exposure to chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
  • Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs.
  • No other concurrent investigational agents are allowed within 2 weeks of enrollment.
  • Known central nervous system metastases, including lymphomatous meningitis
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Nursing women
  • Other active concurrent malignancy (except non-melanoma skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast (DCIS or LCIS). If there is a history of prior malignancy, the patient must be disease-free for ≥ 3-years. Patients whose lymphoma has transformed from a less aggressive histology remain eligible.
  • Patients known to be Human Immunodeficiency Virus (HIV)-positive.
  • Patients with active Hepatitis A, hepatitis B, or hepatitis C infection.
  • Concomitant use of CYP3A4 inhibitors (see Section 13.3)
  • History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity
  • Abnormal coagulation parameters (PT >15 seconds, PTT>40 seconds, and/or INR >1.5) unless related to ongoing anticoagulation treatment required by the patient.
  • Known or suspected hypersensitivity to azacitidine (or any excipients in the formulation) or mannitol.
  • Any known cardiac abnormalities such as:
  • Congenital long QT syndrome
  • QTc interval ≥ 500 millisecond (using the Fridericia formula)
  • Patients taking drugs leading to significant QT prolongation (See Section 13.2)
  • Myocardial infarction within 6 months of C1D1. [Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event, may participate];
  • Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);
  • Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV (see Section 13.4) In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
  • An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
  • Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions (see Section 13.5) and/or ejection fraction <40% by MUGA scan or <50% by echocardiogram and/or MRI;
  • A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest;
  • Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes;
  • Uncontrolled hypertension, i.e., blood pressure (BP) of ≥160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or
  • Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Craig Portell, MD contact

434-924-9637

cp4ys@uvahealth.org

Marian Abdelmalek, MS contact

434-924-8827

mka6s@uvahealth.org

6 sites in 1 country

United States6 sites, 6 recruiting

  • University of Virginia

    Charlottesville, Virginia, 22911

    Marian Abdelmalek, MS, 434-924-8827, mka6s@uvahealth.org

    Craig Portell, MD

    Recruiting

  • The Ohio State University

    Columbus, Ohio, 43210

    Jonathan Brammer, MD, Jonathan.Brammer@osumc.edu

    Not yet recruiting

  • Duke University

    Durham, North Carolina, 27710

    Jie Wang, MD, 919-684-8964, jie.wang416@duke.edu

    Juliana Turner, julianna.turner@duke.edu

    Recruiting

  • VA Long Beach Health Care System

    Long Beach, California, 90822

    Helen MA, MD, 562-826-8000 ext. 1-3906, helen.ma@va.gov

    Pankaj Gupta, MD, 562-826-8000 ext. 1-2243, pankaj.gupta@va.gov

    Recruiting

  • Yale Cancer Center

    New Haven, Connecticut, 06520

    Francesca Montanari, MD, 475-241-1338, francesca.montanari@yale.edu

    Kylie Boyhen, 203-752-7835, kylie.boyhen@yale.edu

    Recruiting

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

    Suchitra Sundaram, MD, 212-824-7377, suchitra.sundaram@mssm.edu

    Martine van Voorthuysen, 646-745-6092, martine.VanVoorthuysen@mssm.edu

    Recruiting

Other trials in United States

About this study

Official title: A Randomized, Phase IIB, Multicenter, Trial of Oral Azacytidine Plus Romidepsin Versus Investigator's Choice in Patients With Relapse or Refractory Peripheral T-cell Lymphoma (PTCL)

The purpose of this study is to find out whether the combination treatment of romidepsin and oral azacytidine is safe and effective in patients with Peripheral T-Cell Lymphoma (PTCL). This study will compare the experimental combination treatment of romidepsin and oral azacytidine to single agent drugs already determined effective in patients with PTCL. For the purposes of this study, the single agent drugs already used to treat lymphoma are called investigator's choice (IC), meaning the investigator will choose which one of these drugs to administer. The IC drug options include romidepsin, belinostat, pralatrexate or gemcitabine given alone. Funding Source: FDA OOPD.

Read the detailed description

Peripheral T-Cell Lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma (NHL) originating from mature (or post-thymic or 'peripheral') T- lymphocytes and NK cells. They are considered very aggressive and are often resistant to conventional chemotherapy.

This study employs a stratified randomization with equal allocation within strata of patients to receive oral 5-azacytidine (AZA) plus romidepsin (ROMI) versus pre-specified investigator choice (ROMI, belinostat, pralatrexate or gemcitabine), for the treatment of relapsed or refractory (R/R) PTCL. The dose and schedule of AZA/ROMI has been determined from a phase I clinical trial of the combination. The primary objective of this study is to estimate the progression free survival (PFS) among patients receiving the combination compared to single agent of choice.

Conditions
PTCL
Being tested
Azacytidine, Romidepsin, Belinostat, Pralatrexate, Gemcitabine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzacytidineDrug

    Also called Vidaza

    Azacytidine, 300 mg po daily on Days 1-14

  • RomidepsinDrug

    Also called Istodax

    Romidepsin, 14 mg/m2 as an intravenous infusion over 4 hours on Days 8, 15, and 22 of a 35-day cycle

  • BelinostatDrug

    Also called Beleodaq

    Belinostat, 1000 mg/m2 as an intravenous infusion over 30 minutes on Days 1-5 every 21 days.

  • PralatrexateDrug

    Also called Folotyn

    Pralatrexate, 30 mg/m2 as an intravenous infusion over a 3-5 minute push once weekly for 6 weeks of a 7 week treatment cycle.

  • GemcitabineDrug

    Also called Gemzar

    Gemcitabine, 1000 mg/m2 as an intravenous infusion over 30 minutes on Days 1, 8, and 15 of a 28 day cycle.

Study groups in NCT04747236
Study groupRoleWhat they receive
AZA and ROMIExperimentalOral Azacytidine (AZA) (300 mg daily on days 1-14) plus Romidepsin (ROMI) (14 mg/m2 as an intravenous infusion over 4 hours +/- 30 minutes on days 8, 15 and 22 of a 35-day cycle.
Receives: Drug: Azacytidine; Drug: Romidepsin
Investigator's ChoiceActive comparatorInvestigator's choice to include: ROMI, 14 mg/m2 IV infusion on days 1, 8, and 15 of a 28 day cycle, belinostat,1000 mg/m2 IV infusion on days 1-5 every 21 days, pralatrexate, 30 mg/m2 IV push once weekly for 6 weeks of a 7-week treatment cycle, or gemcitabine, 1000 mg/m2 IV infusion on days 1, 8, and 15 of a 28-day cycle.
Receives: Drug: Romidepsin; Drug: Belinostat; Drug: Pralatrexate; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

    Difference in progression free survival in subjects treated with AZA/ROMI versus pre-specified investigator choice.

    Measured: Day of randomization to day of progression or death, whichever comes first; or date of last disease assessment or date of transition to other treatment for those without an event, up to 72 weeks.

Secondary outcomes (6)

  1. Overall survival

    Difference in overall survival in subjects treated with AZA/ROMI versus pre-specified investigator choice.

    Measured: Day of randomization to day of death, whichever comes first; or date of last contact for those without an event, up to 72 weeks.

  2. Complete response rate

    Difference in complete response (CR) rate in subjects treated with AZA/ROMI versus pre-specified investigator choice, based on the Revised Criteria for Response Assessment.

    Measured: Day of first objective response to 8 weeks following last dose of study treatment

  3. Overall response rate

    Difference in overall response (OR) rate in subjects treated with AZA/ROMI versus pre-specified investigator choice, based on the Revised Criteria for Response Assessment.

    Measured: Day of first objective response to 8 weeks following last dose of study treatment

  4. Duration of response rate

    Difference in duration of response (DOR) rate in subjects treated with AZA/ROMI versus pre-specified investigator choice, based on the Revised Criteria for Response Assessment.

    Measured: Day of first objective response to day of progression or death, whichever comes first; or date of last disease assessment or date of transition to other treatment for those without an event, up to 72 weeks.

  5. Time to progression

    Difference in time to progression in subjects treated wtih AZA/ROMI versus pre-specified investigator choice.

    Measured: Day of randomization to day of progression, or date of last disease assessment or date of transition to other treatment for those without an event, up to 72 weeks.

  6. Frequency of adverse events

    Frequency of adverse events in subjects treated wtih AZA/ROMI versus prespecified investigator choice assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: From time of informed consent until 90 days after the last day of study treatment for all adverse events or anytime for serious adverse events considered related to the study intervention, through study completion, an average of 18 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2021
  2. Study start19 Feb 2021
  3. Primary completion2 Jun 2028 (estimated)
  4. Study completion2 Jun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04747236
Sponsor's protocol ID
PTCL-001
Other IDs
FD-R-006814-01
Acronym
PTCL
Status last verified
Jan 2026
First submitted
3 Feb 2021
Last updated
21 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Wang K, Shen Y, Hu C, Xu F, Wang Q, Gao Y, Zhou L. Population Pharmacokinetics and Exposure-Response Analysis of Serplulimab in Small Cell Lung Cancer Patients. Clin Transl Sci. 2025 Sep;18(9):e70322. doi: 10.1111/cts.70322.

    PubMed 40932107

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacytidine, Romidepsin and Belinostat in people with PTCL, run by University of Virginia at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Craig Portell, MD (434-924-9637, cp4ys@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (time frame: Day of randomization to day of progression or death, whichever comes first; or date of last disease assessment or date of transition to other treatment for those without an event, up to 72 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04747236, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.

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