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

NCT04747236 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PTCL-001FD-R-006814-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

Brief 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). 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.

Conditions

PTCL

Outcome Measures

Primary Outcomes (1)

• Progression free survival

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

  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)

• Overall survival

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

• Complete response rate

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

• Overall response rate

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

• Duration of response rate

  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.

• Time to progression

  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.

Study Arms (2)

AZA and ROMI

EXPERIMENTAL

Oral 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.

Drug: Azacytidine; Drug: Romidepsin

Investigator's Choice

ACTIVE COMPARATOR

Investigator'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.

Drug: Romidepsin; Drug: Belinostat; Drug: Pralatrexate; Drug: Gemcitabine

Interventions

Azacytidine DRUG

Azacytidine, 300 mg po daily on Days 1-14

Also known as: Vidaza

AZA and ROMI

Romidepsin DRUG

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

Also known as: Istodax

AZA and ROMI; Investigator's Choice

Belinostat DRUG

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

Also known as: Beleodaq

Investigator's Choice

Pralatrexate DRUG

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.

Also known as: Folotyn

Investigator's Choice

Gemcitabine DRUG

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

Also known as: Gemzar

Investigator's Choice

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Virginia: lead
• Celgene: collaborator

Study Sites (6)

VA Long Beach Health Care System

Long Beach, California, 90822, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

NOT YET RECRUITING

University of Virginia

Charlottesville, Virginia, 22911, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 40932107 DERIVED

MeSH Terms

Interventions

Azacitidine; romidepsin; belinostat; 10-propargyl-10-deazaaminopterin; Gemcitabine

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Deoxycytidine

Study Officials

• Craig Portell, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Craig Portell, MD

CONTACT

434-924-9637; cp4ys@uvahealth.org

Marian Abdelmalek, MS

CONTACT

434-924-8827; mka6s@uvahealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Section Head for Hem Malignancies

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: February 10, 2021
• Study Start: February 19, 2021
• Primary Completion (Estimated): June 2, 2028
• Study Completion (Estimated): June 2, 2030
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

US (6)