Study of the Safety and Tolerability of PCI-24781 in Patients With Lymphoma (PCYC-0403)

Tracking Information
First Submitted Date ICMJE	July 28, 2008
First Posted Date ICMJE	July 30, 2008
Results First Submitted Date	February 27, 2014
Results First Posted Date	April 7, 2014
Last Update Posted Date	April 7, 2014
Study Start Date ICMJE	July 2008
Actual Primary Completion Date	November 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 27, 2014)	Phase I (Dose Escalation Phase): MTD and DLTs of PCI-24781 Administered Twice Daily (BID) Measure: Disease Response [ Time Frame: From the Date of PCI-24781 first administration to Cycle 2 Day 1 ]Number of patients experienced DLT in each cohort; Phase II: Overall Response Rate (CR+PR) [ Time Frame: From first response assessment (day 22 to 28 of Cycle 2) to last response assessment on day 22-28 in even-numbered cycles ]
Original Primary Outcome Measures ICMJE; (submitted: July 28, 2008)	Measure: Dose limiting toxicity assessment for each patient at the end of the first 28 day cycle (Phase 1) Measure: Disease response [ Time Frame: At the end of every 2 cycle ]
Change History	Complete list of historical versions of study NCT00724984 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE; (submitted: July 28, 2008)	Measure: Adverse event assessed through 30 days after last dose of study drug Measure: Pharmacokinetic/Pharmacodynamic assessments [ Time Frame: After every 2 cycle ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Study of the Safety and Tolerability of PCI-24781 in Patients With Lymphoma
Official Title ICMJE	Phase I/II Dose-Escalation Study of the Pan-Histone Deacetylase (HDAC) Inhibitor PCI-24781 in Lymphoma
Brief Summary	The first part of the study will determine the highest dose of study drug that can be taken without causing serious side effects in patients with lymphoma. The appropriate dose determined from the first part of the study will be used in the second part of the study to assess disease response in 2 different types of lymphoma patients.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin
Intervention ICMJE	Drug: PCI-24781; Phase I Dose Escalation: Up to 5 cohorts will receive PCI-24781 orally at doses starting at 30mg/m2 two times a day approximately 4-6 hours apart ("BID"), up to 90mg/m2 administered 5 days/week during the first 21 days of each 28 day cycle until the maximum tolerated dose (MTD) is reached. If a dose limiting toxicity (DLT) occurs, then the next cohort will receive PCI-24781 BID for 7 days every other week (2 times in a 28 day cycle). Phase II Efficacy Evaluation: All patients will receive PCI-24781 orally at the dosage and regimen determined in Phase I.
Study Arms	Experimental: 1; Intervention: Drug: PCI-24781
Publications *	Buggy JJ, Cao ZA, Bass KE, Verner E, Balasubramanian S, Liu L, Schultz BE, Young PR, Dalrymple SA. CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther. 2006 May;5(5):1309-17.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 27, 2014)	55
Original Estimated Enrollment ICMJE; (submitted: July 28, 2008)	126
Study Completion Date	Not Provided
Actual Primary Completion Date	November 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00724984
Other Study ID Numbers ICMJE	PCYC-0403
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Pharmacyclics LLC.
Study Sponsor ICMJE	Pharmacyclics LLC.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Thorsten Graef, MD Pharmacyclics LLC.
PRS Account	Pharmacyclics LLC.
Verification Date	February 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP