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Study of the Safety and Tolerability of PCI-32765 in Patients With Recurrent B Cell Lymphoma (PCYC-04753)
This study is currently recruiting participants.
Verified by Pharmacyclics, June 2010
First Received: February 20, 2009   Last Updated: July 27, 2010   History of Changes
Sponsor: Pharmacyclics
Information provided by: Pharmacyclics
ClinicalTrials.gov Identifier: NCT00849654
  Purpose

The purpose of this study is to establish the safety and optimal dose of orally administered PCI-32765 in patients with recurrent B cell lymphoma.


Condition Intervention Phase
B-Cell Lymphoma
B-Cell Leukemia
Drug: PCI-32765
Phase I

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Control: Uncontrolled
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose-Escalation Study of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Recurrent B Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • Dose limiting toxicity assessment for each patient. [ Time Frame: At the end of the first 35 day cycle ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic/ Pharmacodynamic assessments [ Time Frame: during Cycle 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response [ Time Frame: at the end of Cycles 2, 4, and 6 ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: February 2009
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
PCI-32765: Experimental Drug: PCI-32765
PCI-32765 will be administered in 1.25, 2.5, 5.0, 8.3, 12.5, and 17.5 mg/kg/d dose cohorts orally once per day for 28 days followed by a 7 day rest period. Six patients will be enrolled in each dosing cohort. If ≥ 2 DLTs occur in any cohort, the MTD will be established as the previous dosing cohort. If MTD is not reached, dosing levels may be increased beyond 17.5 mg/kg/d by 33% increments. The study will continue until the MTD has been established. Patients who do not experience DLT during Cycle 1 may continue with additional cycles of 28 day PCI-32765 treatment followed by a 7 day rest period for a maximum of six cycles provided that there is no disease progression or DLT.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women and men ≥ 18 years of age. There is no experience with this drug in a pediatric population.
  • Body weight ≥ 40 kg.
  • Recurrent surface immunoglobulin positive B cell non-Hodgkin's lymphoma (according to WHO classification) including small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL).
  • Bi-dimensional measurable disease (≥ 2 cm diameter or for CLL ≥ 4000 leukemia cells/mm3).
  • Have failed ≥ 1 previous treatment for lymphoma and no standard therapy is available. Patients with diffuse large B cell lymphoma must have failed, refused or be ineligible for autologous stem cell transplant.
  • ECOG performance status of ≤ 1.
  • Ability to swallow oral capsules without difficulty.
  • Willing and able to sign a written informed consent.

Exclusion Criteria:

  • More than four prior systemic therapies (not counting maintenance rituximab). Salvage therapy/conditioning regimen leading up to autologous bone marrow transplantation is considered to be one regimen.
  • Prior 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 involvement by lymphoma.
  • Active opportunistic infection or treatment for opportunistic infection within 4 weeks before first day of study drug dosing.
  • History of malabsorption.
  • Laboratory abnormalities:
  • Creatinine > 1.5 × institutional upper limit of normal (ULN)
  • Total bilirubin > 1.5 x institutional ULN (unless elevated from documented Gilbert's syndrome)
  • AST or ALT > 2.5 × institutional ULN
  • Platelet count < 75,000/µL
  • Absolute neutrophil count (ANC) < 1500/µL.
  • 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 medications known to prolong QTc interval or that may be associated with Torsades de Pointes within 7 days of treatment start (see Appendix C).
  • 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.
  • 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.
  • History of prior cancer < 5 years ago, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00849654

Contacts
Contact: Sara Rodriguez 408-215-3455 srodriguez@pcyc.com
Contact: Raquel Izumi, PhD 408-215-3341 rizumi@pcyc.com

Locations
United States, Arizona
TGen Clinical Research Services at Scottsdale Healthcare Terminated
Scottsdale, Arizona, United States, 85258
United States, California
Stanford University School of Medicine Recruiting
Palo Alto, California, United States, 94305
Contact: Sipra Choudhury     650-736-2563     schoudhury@stanford.edu    
Principal Investigator: Ranjana Advani, MD            
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Angela Cisneros     773-834-0475     acisnero@medicine.bsd.uchicago.edu    
Principal Investigator: Sonali Smith, MD            
United States, Maryland
National Cancer Institute Recruiting
Bethesda, Maryland, United States, 20892-1203
Contact: Therese White     301-402-5886     whiteth@mail.nih.gov    
Principal Investigator: Wyndham Wilson, MD            
United States, New York
New York Prebyterian Hospital Cornell Medical Center Recruiting
New York, New York, United States, 10065
Contact: Julia Morrison     212-746-5269     jum2020@med.cornell.edu    
Principal Investigator: Richard Furman, MD            
United States, Oregon
Willamette Valley Cancer Institute/Research Ctr Recruiting
Eugene, Oregon, United States, 97401
Contact: Jeanne Schaffer     541-683-5001     jeanne.schaffer@usoncology.com    
Principal Investigator: Jeff P Sharman, MD            
United States, Texas
University of Texas, MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Justin Cummings     713-792-8785     jjcummings@mdanderson.org    
Principal Investigator: Nathan Fowler, MD            
United States, Vermont
University of Vermont College of Medicine Recruiting
Burlington, Vermont, United States, 05405
Contact: Karen Lepsuchenko     802-656-9924     lepuschenko@uvm.edu    
Principal Investigator: Barbara Grant, MD            
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Contact: Tracy Harding, RN     757-213-5658     tracy.harding@usoncology.com    
Principal Investigator: Paul Conkling, MD            
United States, Washington
Northwest Cancer Specialists, Vancouver Cancer Center Recruiting
Vancouver, Washington, United States, 98684
Contact: Judy Welch, RN     360-449-6522     judith.welch@usoncology.com    
Principal Investigator: Kate Kolibaba, MD            
Yakima Valley Memorial Hospital/North Star Lodge Cancer Ctr Recruiting
Yakima, Washington, United States, 98902
Contact: Beth Parker, CRC     509-574-3493     bethparker@yvmh.org    
Principal Investigator: Thomas Boyd, MD            
Sponsors and Collaborators
Pharmacyclics
Investigators
Study Director: Ahmed Hamdy, MD Pharmacyclics
  More Information

Additional Information:
No publications provided

Responsible Party: Pharmacyclics ( Ahmed Hamdy, MD )
ClinicalTrials.gov Identifier: NCT00849654     History of Changes
Other Study ID Numbers: PCYC-04753
Study First Received: February 20, 2009
Last Updated: July 27, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Pharmacyclics:
PCI-32765
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Burkitt Lymphoma
Lymphoma, B-Cell, Marginal Zone
Lymphoma, B-Cell, Diffuse
Lymphoma, Follicular
Lymphoma, Mantle Cell
Leukemia, Lymphoid
Leukemia, B-Cell
Waldenstrom macroglobulinemia
Bruton's Tyrosine Kinase

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on September 07, 2010