Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

Clinical trial: Romidepsin in Treating Patients With Steroid-Refractory Graft-versus-Host Disease

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: 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

Relevance to patient case: not relevant