INCLUSION CRITERIA:
Patients must fulfill all of the following criteria to be eligible for study participation and
have:
Histologically confirmed PTCL NOS, angioimmunoblastic T-cell lymphoma, extranodal NK/T-cell lymphoma nasal type, enteropathy- type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous gamma T-cell lymphoma, hepatosplenic T-cell lymphoma, ALCL (ALK-1 negative), or patients with ALK-1 expressing ALCL (ALK-1 positive) who have relapsed disease after ASCT;
Age greater than or equal to18 years;
Written informed consent;
PD following at least one systemic therapy or refractory to at least one prior systemic therapy;
Measurable disease according to the IWC criteria and/or measurable cutaneous disease;
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
Serum potassium greater than or equal to 3.8 mmol/L and magnesium greater than or equal to 0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria);
Negative urine or serum pregnancy test on females of childbearing potential; and
All women of childbearing potential must use an effective barrier method of contraception (either an intrauterine contraceptive device (IUCD) or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter. Male patients should use a barrier method of contraception during the treatment period and for at least 1 month thereafter. Hormonal methods of contraception such as the contraceptive pill or patch (particularly those containing ethinyl-estradiol) should be avoided due to a potential drug interaction.
EXCLUSION CRITERIA:
Patients are ineligible for entry if any of the following criteria are met:
Known central nervous system (CNS) lymphoma [computed tomography (CT) or magnetic resonance imaging (MRI) scans are required only if brain metastasis is suspected clinically);
Chemotherapy or immunotherapy within 4 weeks of study entry (6 weeks if nitrosoureas given);
Concomitant use of any other anti-cancer therapy;
Concomitant use of any investigational agent;
Use of any investigational agent within 4 weeks of study entry;
Any known cardiac abnormalities such as:
Congenital long QT syndrome;
QTcF interval greater than 480 milliseconds (msec);
A myocardial infarction within 12 months of study entry;
Other significant ECG abnormalities including 2nd atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
A history of 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 significant ST depression (ST depression of greater than or equal to 2 mm, measured from isoelectric line to the ST segment at a point 60 msec at the end of the QRS complex). 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 (see Appendix F) and/or ejection fraction less than 40 percent by MUGA scan or less than 50 percent by echocardiogram and/or MRI;
A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently
INCLUSION CRITERIA:
Patients with Grad 3 or 4 toxicities from prior chemotherapy should recover to Grad 2 or less before enrolling on the protocol. This excludes laboratory or hematological toxicities as these are detailed in Sections 4.2 and 4.3 of the protocol. Patients with non-life threatening neurologic toxicities from prior chemotherapy may be considered eligible for the perotocol if they otherwise meet protocol entry criteria.
EXCLUSION CRITERIA:
Patients seropositive for hepatitis B surface Ag positive, or hepatitis C
Absolute neutrophil cound (ANC) less than or equal to 1.0 time 10(9) cells/L. Patients with neutropenia (ANC 1-1.5) as a result of bone marrow involvement with their disease may be supported with granulocyte-colony stimulating factor (G-CSF)
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009