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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00724984
Recruitment Status : Completed
First Posted : July 30, 2008
Results First Posted : April 7, 2014
Last Update Posted : April 7, 2014
Information provided by (Responsible Party):
Pharmacyclics LLC.

July 28, 2008
July 30, 2008
February 27, 2014
April 7, 2014
April 7, 2014
July 2008
November 2012   (Final data collection date for primary outcome measure)
  • 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 ]
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 ]
Complete list of historical versions of study NCT00724984 on Archive Site
Not Provided
Measure: Adverse event assessed through 30 days after last dose of study drug Measure: Pharmacokinetic/Pharmacodynamic assessments [ Time Frame: After every 2 cycle ]
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Study of the Safety and Tolerability of PCI-24781 in Patients With Lymphoma
Phase I/II Dose-Escalation Study of the Pan-Histone Deacetylase (HDAC) Inhibitor PCI-24781 in Lymphoma
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.
Not Provided
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Lymphoma
  • Hodgkin Disease
  • Lymphoma, Non-Hodgkin
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.

Experimental: 1
Intervention: Drug: PCI-24781
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 Identifier (NCT Number) in Medline.
Not Provided
November 2012   (Final data collection date for primary outcome measure)

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:

      1. Follicular non-Hodgkin's Lymphoma
      2. 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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
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Pharmacyclics LLC.
Pharmacyclics LLC.
Not Provided
Study Director: Thorsten Graef, MD Pharmacyclics LLC.
Pharmacyclics LLC.
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP