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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.

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.

Condition or disease Intervention/treatment Phase
Lymphoma Hodgkin Disease Lymphoma, Non-Hodgkin Drug: PCI-24781 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Dose-Escalation Study of the Pan-Histone Deacetylase (HDAC) Inhibitor PCI-24781 in Lymphoma
Study Start Date : July 2008
Actual Primary Completion Date : November 2012

Arm Intervention/treatment
Experimental: 1 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.

Primary Outcome Measures :
  1. 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

  2. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00724984

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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Illinois
Northwestern University Medical School
Chicago, Illinois, United States, 60611
United States, Indiana
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
United States, Massachusetts
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, Vermont
University of Vermont and Fletcher Allen Health Care
Burlington, Vermont, United States, 05405
Sponsors and Collaborators
Pharmacyclics LLC.
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Study Director: Thorsten Graef, MD Pharmacyclics LLC.

Additional Information:
Publications of Results:
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Responsible Party: Pharmacyclics LLC. Identifier: NCT00724984     History of Changes
Other Study ID Numbers: PCYC-0403
First Posted: July 30, 2008    Key Record Dates
Results First Posted: April 7, 2014
Last Update Posted: April 7, 2014
Last Verified: February 2014

Keywords provided by Pharmacyclics LLC.:
Hodgkin Disease
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral

Additional relevant MeSH terms:
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Hodgkin Disease
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action