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

NCT ID: NCT02203578

Last Updated: 2017-03-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2016-06-14

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.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Supportive care (romidepsin)

Patients receive romidepsin 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.

Group Type: EXPERIMENTAL

romidepsin

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

romidepsin

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

FK228; FR901228; Istodax

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

• 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

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Rutgers Cancer Institute of New Jersey

OTHER

Sponsor Role: collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roger Strair

Role: PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Locations

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Countries

United States

Other Identifiers

NCI-2014-01411

Identifier Type: REGISTRY

Identifier Source: secondary_id

021309

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA072720

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro2014004116

Identifier Type: OTHER

Identifier Source: secondary_id

021309

Identifier Type: -

Identifier Source: org_study_id