Depsipeptide to Treat Patients With Cutaneous T-Cell Lymphoma and Peripheral T-Cell Lymphoma

Completed · Phase 2

Conditions studied: Cutaneous T Cell Lymphoma, Peripheral T Cell Lymphoma

In brief

Background: NSC630176 is a depsipeptide fermentation product from Chromobacterium violaceum with potent cytotoxic activity against human tumor cell lines and in vivo efficacy against both human tumor xenografts and murine tumors (1-3). NSC 630176, herein referred to as depsipeptide, shows a lack of cross resistance with several commonly used cytotoxic agents such as vincristine, 5-fluorouracil, mitomycin C and cyclophosphamide (2). However, it has been defined as a P-glycoprotein (Pgp) substrate by COMPARE analysis of the National Cancer Institute (NCI) drug screen cytotoxicity profile (4). Depsipeptide is a member of a novel class of antineoplastic agents, the histone deacetylase inhibitors. In the phase I trial conducted at the National Cancer Institute (NCI), responses were observed at the maximum tolerated dose (MTD) in patients with cutaneous and peripheral T-cell lymphoma. Objectives: In patients with cutaneous T-cell lymphoma, the primary end points to be examined are overall response rate, complete response rate and duration of response. In patients with relapsed peripheral T-cell lymphoma, the endpoints to be examined are overall response rate and complete response rate. To evaluate the tolerability of depsipeptide with extended cycles of therapy. Eligibility: Patients with cutaneous T-cell lymphoma (mycosis fungoides or Sezary syndrome) or other peripheral T-cell lymphomas are eligible. Design: Depsipeptide will be administered at 14 mg/m\^2, over 4 hours on days 1, 8 and 15. This trial will accrue in six cohorts; Arm 1, patients with cutaneous T-cell lymphoma who have had less than or equal to two prior cytotoxic chemotherapy regimens; Arm 2, patients with peripheral T-cell lymphoma who have had less than or equal to two prior cytotoxic chemotherapy regimens; Arm 3, patients with cutaneous and peripheral T-cell lymphoma who have had more than two prior cytotoxic chemotherapy regimens; Arm 4, patients with other mature T-cell lymphomas; Arm 5, a replicate arm of arm 1; Arm 6, patients with peripheral T-cell lymphoma who have had more than two prior cytotoxic chemotherapy regimens; Arm 7, patients with cutaneous T cell lymphoma who have received vorinostat. Dose may be adjusted based on toxicities.

Key facts

Study ID: NCT00007345
Run by: National Cancer Institute (NCI)
People needed: 131
Starts: 2001-03-08
Expected to finish: 2015-07-27
Last updated by the study team: 2017-05-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients with unconfirmed diagnosis, or with B-cell lymphomas will be excluded.
Prior or concurrent malignancies that have not been curatively treated.
Known central nervous system (CNS) lymphoma.
Chemotherapy within 4 weeks, 6 weeks for nitrosoureas or mitomycin C.
Biologics, Immunotherapy within 2 weeks.
Human Immunodeficiency virus (HIV) seropositivity.
Pregnant or breast-feeding patients.
Major surgery within 21 days.
Uncontrolled infection or uncontrolled medical illness.
Patients having received prior histone deacetylase (HDAC) inhibitor therapy for T cell lymphoma will be excluded except for patients eligible to enroll in cohort 7.
Patients with the following cardiac risk factors will be excluded from the study:
Patients with known cardiac abnormalities such as:
Congenital long QT syndrome
Corrected QT interval (QTc) interval greater than 480 milliseconds
Patients who have had a myocardial infarction within 12 months of study entry.
Patients who have active coronary artery disease as, e.g. angina as defined by Canadian Class II-IV
Patients with an electrocardiography (ECG) recorded at screening showing evidence of cardiac ischemia (ST depression of greater than or equal to 2 mm).
Any patient in whom coronary artery disease is suspected should be referred for a cardiology consultation and if active myocardial ischemia is demonstrated the patient should be excluded. If a noninvasive imaging study is equivocal, it may be necessary to proceed to coronary angiography.
Patients with congestive heart failure that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction less than 45% by MUGA scan or less than 50% by echocardiogram and/or MRI.
Patients with a history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD). Patients with a history of arrhythmia should have Holter monitoring and evaluation by cardiology.
Patients with dilated, hypertrophic, or restrictive cardiomyopathy from prior treatment or other causes (in doubt, see ejection fraction criteria above). Patients with left ventricular hypertrophy should be discussed with the Principal Investigator or Study Chairman.
Patients with uncontrolled hypertension, i.e., systolic blood pressure (SBP) greater than or equal to 160 mm Hg or diastolic blood pressure (DBP) greater than or equal to 95 mm Hg.
Patients with cardiac arrhythmia requiring anti-arrhythmic medication other than beta blocker or calcium channel blocker. Patients in whom digitalis cannot be discontinued are excluded from study.
Patients with Mobitz II second degree heart block who do not have a pacemaker. Patients with first degree or Mobitz I second degree heart block, bradyarrhythmias or sick sinus syndrome require Holter monitoring and evaluation by cardiology.
Patients with other cardiac disease may be excluded at the discretion of the principal investigator (PI) following consultation with cardiology.

Where it is running

Mayo Clinic Scottsdale — Scottsdale, Arizona, United States
University of Arkansas — Little Rock, Arkansas, United States
City of Hope National Cancer Center — Duarte, California, United States
Mercy General Hospital — Sacramento, California, United States
Georgetown University — Washington D.C., District of Columbia, United States
Northwestern University — Chicago, Illinois, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States
North Shore University Hospital — Manhasset, New York, United States
University of Pittsburgh — Pittsburgh, Pennsylvania, United States
West Virginia University — Morgantown, West Virginia, United States
Royal Adelaide Hospital — Adelaide, Australia
Peter MacCallum Cancer Centre — Melbourne, Australia
Sir Charles Gairdner Hospital — Perth, Australia

Full record on ClinicalTrials.gov

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