A Safety and Tolerability Study of PCI-24781 in Subjects With Cancer

A Long-term Safety Study of the Pan-histone Deacetylase (HDAC) Inhibitor, PCI-24781, in Subjects With Cancer

The purpose of this study is to determine the long-term (> 6 months) safety of PCI 24781 PO in subjects with lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Leukemia; Multiple Myeloma; Hodgkin Disease; Non-Hodgkin's Lymphoma; Lymphocytic
• Intervention / Treatment: Drug: PCI-24781

Detailed Description

An open-label, monotherapy, multicenter, extension study open to subjects who have derived benefit from PCI 24781 PO for at least 6 months and want to continue receiving study drug.

Subjects enrolled in this study will receive PCI-24781 at the schedule and dosage from their prior protocol. Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Univ. Med School
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • Univ. of Nebraska Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

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:

1. Men and women with cancer that did not progress while treated with PCI 24781 PO for at least 6 months and who want to continue receiving study drug
2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
3. Agreement to use contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear children
4. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
5. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Exclusion Criteria:

1. A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of oral PCI-24781, or put the study outcomes at undue risk
2. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
3. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
4. Immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone > 20 mg/day) or experimental therapy (other than PCI-24781 PO) within 4 weeks before first dose of study drug
5. Concomitant use of medicines known to cause QT prolongation or torsades de points (see Appendix 2)
6. Central nervous system involvement by lymphoma
7. Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection
8. Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5 x ULN (unless due to Gilbert's disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
9. Lactating or pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCI-24781	Drug: PCI-24781; Subjects enrolled in this study will receive PCI-24781 administered orally at the schedule and dosage from their prior protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	frequency, severity and relatedness of adverse events	30 days after last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response	tumor response will be assessed per established response criteria. This study will capture time to disease progression and duration of response.	frequency of tumor assessments done per standard of care

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: June 21, 2010
• First Submitted That Met QC Criteria: June 22, 2010
• First Posted (Estimate): June 23, 2010

Study Record Updates

• Last Update Posted (Estimate): June 19, 2013
• Last Update Submitted That Met QC Criteria: June 17, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Lymphoma; Leukemia; Chronic; Hodgkin Disease; Lymphocytic; Non-Hodgkin's; PCI-24781
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Lymphoma; Multiple Myeloma; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Histone Deacetylase Inhibitors; Abexinostat
• Other Study ID Numbers: PCYC-0405-CA; PCI-24781 (Registry Identifier: 69451)