Clinical trial NCT02203578: Romidepsin in Treating Patients With Steroid-Refractory Graft-versus-Host Disease
Official title: A Pilot Study of Romidepsin for Therapy of Graft-versus-Host Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Graft Versus Host Disease
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Rutgers Cancer Institute of New Jersey
First posted: 2014-07-30
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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 graft-versus-host disease caused by a bone marrow or stem cell transplant.

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 days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3 and 6 months.

Eligibility criteria: Inclusion Criteria:

* 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 Criteria:

* 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

Primary outcomes:
measure: Incidence of aGVHD
timeFrame: At 28 days after initiation of romidepsin
measure: Incidence of cGVHD
timeFrame: At 1 month after initiation of romidepsin
measure: Incidence of cGVHD
timeFrame: At 3 months after initiation of romidepsin
measure: Incidence of cGVHD
timeFrame: At 6 months after initiation of romidepsin
measure: Incidence of cGVHD
timeFrame: At 9 months after initiation of romidepsin
measure: Incidence of cGVHD
timeFrame: At 12 months after initiation of romidepsin
Secondary outcomes:
measure: Total Duration of Immunosuppressive Therapy
timeFrame: Up to 12 months after initiation of romidepsin
measure: Rate of Documented Infection
timeFrame: Up to 12 months after initiation of romidepsin
measure: T Cell Kinetics - Reconstitution
timeFrame: Up to 12 months after initiation of romidepsin
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Roger Strair
role: PRINCIPAL_INVESTIGATOR
References: