RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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)

Quick Facts

Study Start:2021-02-19

Study Completion:2028-06-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04747236

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. 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. 2. Patients with anaplastic large cell lymphoma are required to have received brentuximab vedotin (Bv) prior to study enrollment. 3. Measurable Disease as defined in Section 8.1.3.1. 4. Age ≥18 years. 5. ECOG performance status ≤2 6. Patients must have adequate organ and marrow function as defined below: 7. Negative urine or serum pregnancy test for females of childbearing potential 8. All females of childbearing potential and male subjects must agree to use an effective method of contraception (see section 5.4 for more details) 9. Be willing and able to provide written consent or assent for the trial.	1. Diagnosis of patch/plaque stage mycosis fungoides 2. 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. 3. Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs. 4. No other concurrent investigational agents are allowed within 2 weeks of enrollment. 5. Known central nervous system metastases, including lymphomatous meningitis 6. 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. 7. Nursing women 8. 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. 9. Patients known to be Human Immunodeficiency Virus (HIV)-positive. 10. Patients with active Hepatitis A, hepatitis B, or hepatitis C infection. 11. Concomitant use of CYP3A4 inhibitors (see Section 13.3) 12. 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 13. Abnormal coagulation parameters (PT \>15 seconds, PTT\>40 seconds, and/or INR \>1.5) unless related to ongoing anticoagulation treatment required by the patient. 14. Known or suspected hypersensitivity to azacitidine (or any excipients in the formulation) or mannitol. 15. 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)

Inclusion Criteria

Exclusion Criteria

1. 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.
2. Patients with anaplastic large cell lymphoma are required to have received brentuximab vedotin (Bv) prior to study enrollment.
3. Measurable Disease as defined in Section 8.1.3.1.
4. Age ≥18 years.
5. ECOG performance status ≤2
6. Patients must have adequate organ and marrow function as defined below:
7. Negative urine or serum pregnancy test for females of childbearing potential
8. All females of childbearing potential and male subjects must agree to use an effective method of contraception (see section 5.4 for more details)
9. Be willing and able to provide written consent or assent for the trial.

1. Diagnosis of patch/plaque stage mycosis fungoides
2. 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.
3. Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs.
4. No other concurrent investigational agents are allowed within 2 weeks of enrollment.
5. Known central nervous system metastases, including lymphomatous meningitis
6. 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.
7. Nursing women
8. 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.
9. Patients known to be Human Immunodeficiency Virus (HIV)-positive.
10. Patients with active Hepatitis A, hepatitis B, or hepatitis C infection.
11. Concomitant use of CYP3A4 inhibitors (see Section 13.3)
12. 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
13. Abnormal coagulation parameters (PT \>15 seconds, PTT\>40 seconds, and/or INR \>1.5) unless related to ongoing anticoagulation treatment required by the patient.
14. Known or suspected hypersensitivity to azacitidine (or any excipients in the formulation) or mannitol.
15. 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)

Contacts and Locations

Study Contact

Enrica Marchi, MD

CONTACT

434-924-9637

em5yt@hscmail.mcc.virginia.edu

Marian Abdelmalek, MS

CONTACT

434-924-8827

mka6s@hscmail.mcc.virginia.edu

Principal Investigator

Enrica Marchi, MD

PRINCIPAL_INVESTIGATOR

University of Virginia

Study Locations (Sites)

VA Long Beach Health Care System

Long Beach, California, 90822

United States

Yale Cancer Center

New Haven, Connecticut, 06520

United States

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

United States

Duke University

Durham, North Carolina, 27710

United States

University of Virginia

Charlottesville, Virginia, 22911

United States

Collaborators and Investigators

Sponsor: University of Virginia

Enrica Marchi, MD, PRINCIPAL_INVESTIGATOR, University of Virginia

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-02-19

Study Completion Date2028-06-02

Study Record Updates

Study Start Date2021-02-19

Study Completion Date2028-06-02

Terms related to this study

Additional Relevant MeSH Terms

PTCL