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

February 27, 2014 updated by: Pharmacyclics LLC.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From the Date of PCI-24781 first administration to Cycle 2 Day 1
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
From first response assessment (day 22 to 28 of Cycle 2) to last response assessment on day 22-28 in even-numbered cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pharmacyclics LLC.

Investigators

  • Study Director: Thorsten Graef, MD, Pharmacyclics LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2008

Primary Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

July 28, 2008

First Submitted That Met QC Criteria

July 28, 2008

First Posted (Estimate)

July 30, 2008

Study Record Updates

Last Update Posted (Estimate)

April 7, 2014

Last Update Submitted That Met QC Criteria

February 27, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCYC-0403

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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