Study of the Safety and Tolerability of PCI-24781 in Patients With Lymphoma

Inclusion Criteria:

• age ≥ 18 years

Phase I: Any measurable, histologically confirmed, and previously treated lymphoma

Phase II: Measurable, histologically confirmed, and previously treated lymphoma in one of the following categories:

Follicular non-Hodgkin's Lymphoma
Mantle cell lymphoma
Ability to swallow oral capsules without difficulty
Estimated life expectancy > 12 weeks
ECOG performance status ≤ 1
Willing and able to sign a written informed consent

Exclusion Criteria:

• More than four prior systemic treatment regimens (not counting maintenance rituximab; salvage therapy/conditioning regimen preceding autologous bone marrow transplantation [ABMT] and ABMT count as one regimen)

Allogeneic bone marrow transplant
Immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks before first day of study drug dosing
Major surgery within 4 weeks before first day of study drug dosing
CNS lymphoma or a history of meningeal carcinomatosis
Prior treatment with an HDAC inhibitor (unless for treatment of Mycosis fungoides or Sézary syndrome)
Creatinine > 1.5 x institutional upper limit of normal (ULN) or creatinine clearance ≤ 50 mL/min
Total bilirubin > 1.5 x institutional ULN (unless elevated from documented Gilbert's syndrome)
AST and ALT > 2.5 x institutional ULN
Platelet count < 75,000/µL for Phase I and <100,000>µL for Phase II
Absolute neutrophil count (ANC) < 1500/µL
Malabsorption
Corticosteroids > 20 mg prednisone equivalent per day (topical, inhaled, or nasal corticosteroids are permitted)
Concurrent therapeutic anticoagulation (Phase I only)
Uncontrolled illness including but not limited to: ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements
Risk factors for, or use of drugs known to prolong QTc interval or that may be associated
QTc prolongation (defined as a QTc ≥ 450 msecs) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has a QTc ≥ 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation.
History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within the past 6 months.
For patients with history of myocardial infarction, congestive heart failure, abnormal left ventricular ejection fraction (LVEF), and/or prior anthracycline exposure, LVEF < 50%, as assessed by ventriculography (nuclear or heart catheterization) or echocardiogram, when performed within 28 days of first dose of study drug.
For patients with history of coronary artery disease, a cardiac stress test (either exercise or pharmacologic) that demonstrates clinically significant abnormalities when performed within 28 days of first dose of study drug.
Known HIV infection.
Other medical or psychiatric illness or organ dysfunction which, in the opinion of the investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the study agent.
Pregnant or lactating women (female patients of child-bearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or, if positive, a pregnancy ruled out by ultrasound).
Women of child-bearing potential, or sexually active men, unwilling to use adequate contraceptive protection during the course of the study.