Status:
TERMINATED
Romidepsin in Treating Patients With Steroid-Refractory Graft-versus-Host Disease
Lead Sponsor:
Rutgers, The State University of New Jersey
Collaborating Sponsors:
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
Conditions:
Graft Versus Host Disease
Eligibility:
All Genders
18+ years
Phase:
NA
Brief Summary
This pilot clinical trial studies romidepsin in treating patients with graft-versus-host disease (GVHD) that has not responded to treatment with steroids. Romidepsin may be an effective treatment for ...
Detailed Description
PRIMARY OBJECTIVES: I. To determine if romidepsin should be developed as a therapy for patients with steroid-refractory GVHD. OUTLINE: Patients receive romidepsin intravenously (IV) over 4 hours on...
Eligibility Criteria
Inclusion
- Patients with steroid (or immunosuppressive therapy \[IST\]) refractory acute GVHD (aGVHD) or chronic GVHD (cGVHD)
- Absolute neutrophil count \>= 750/mm\^3
- Platelet count \>= 50,000/mm\^3
- Corrected QT interval (QTc) =\< 480 msec
- Bilirubin =\< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN
- Serum potassium \>= 3.8 mmol/L
- Serum magnesium \>= 1.8 mg/dL
- Serum creatinine =\< 2.0 mg/dl
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3
- Patients may undergo electrolyte repletion therapy to meet eligibility requirements
- Patients must be scheduled for tapering doses of (or no longer treated with):
- Cyclosporine;
- Tacrolimus;
- Sirolimus;
- Steroids (patients may be on physiologic doses of steroids)
- Patients receiving extracorporeal photopheresis must discontinue extracorporeal photopheresis or placed on a tapering schedule;
- Any prior therapy for GVHD must be completed and discontinued with the exception of the above;
- Patients with breakpoint cluster region (bcr)-ABL proto-oncogene 1 (abl) associated malignancies may be on a tyrosine kinase inhibitor as malignant disease therapy or prophylaxis
- There must be no uncontrolled active infections or medical conditions that the investigator feels will compromise the safety of the treatment and/or the assessment of the efficacy of therapy
- The patient must be aware of the high risk and experimental nature of the treatment and provide informed consent
- Negative serum pregnancy test at the time of enrollment for females of childbearing potential
- For males and females of child-producing potential, use of effective contraceptive methods during the study and for at least 6 months after the last dose of romidepsin
Exclusion
- Active/uncontrolled infection
- Evidence of relapsed disease
- Life expectancy \< 12 weeks
- Pregnant or breast feeding females
- Prior therapy with romidepsin
- Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are seropositive because of hepatitis B virus vaccine are eligible
- Any known cardiac abnormalities such as:
- Congenital long QT syndrome
- QTc interval \>= 480 milliseconds;
- Myocardial infarction within 6 months of course 1, day 1 (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 electrocardiogram (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; 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 and/or ejection fraction \< 40% by multi gated acquisition (MUGA) scan or \< 50% by echocardiogram and/or magnetic resonance imaging (MRI);
- A known 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);
- Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other cause;
- Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
- 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
- Patients taking drugs leading to significant QT prolongation must have an ECG prior to each treatment
- Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
- Concomitant use of medications known to induce a disulfiram-like reaction to alcohol
Key Trial Info
Start Date :
November 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 14 2016
Estimated Enrollment :
1 Patients enrolled
Trial Details
Trial ID
NCT02203578
Start Date
November 1 2014
End Date
June 14 2016
Last Update
March 30 2017
Active Locations (1)
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1
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903