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Study of the Safety and Tolerability of PCI-32765 in Patients With Recurrent B Cell Lymphoma (PCYC-04753)

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: NCT00849654
Recruitment Status : Completed
First Posted : February 24, 2009
Last Update Posted : May 22, 2013
Information provided by (Responsible Party):
Pharmacyclics LLC.

Brief Summary:
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 or disease Intervention/treatment Phase
B-Cell Lymphoma B-Cell Leukemia Drug: PCI-32765 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : February 2009
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

Arm Intervention/treatment
Experimental: PCI-32765 Drug: PCI-32765

In the dose-escalation cohorts, PCI-32765 will be administered in 1.25, 2.5, 5.0, 8.3, 12.5, and 17.5 mg/kg/d dose orally once per day for 28 days followed by a 7-day rest period to determine the MTD. If MTD is not reached, dosing levels may be increased beyond 17.5mg/kg/d by 33% increments.

In the continuous dosing cohorts, PCI-32765 will be administered in 8.3 mg/kg/day and 560 mg/day (fixed dose) dose orally once per day for 35 days.

Primary Outcome Measures :
  1. Dose limiting toxicity assessment for each patient. [ Time Frame: At the end of the first 35 day cycle ]
  2. Adverse events [ Time Frame: 30 days after last dose of study drug ]
  3. Pharmacokinetic/ Pharmacodynamic assessments [ Time Frame: during Cycle 1 ]

Secondary Outcome Measures :
  1. Tumor response [ Time Frame: at the end of Cycles 2, 4, and 6 unitl progression ]

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:

  • 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 (NHL) according to WHO classification, including small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL) lymphoplasmacytic lymphoma, including Waldenström's Macroglobulinemia (WM), and pre-identified DLBCL ABC subtype oFor the DLBCL-ABC cohort, documented, activated B-cell subtype by either immunohistochemistry or tissue microarray analysis.
  • Measurable disease (for NHL, bidimensional disease ≥ 2 cm diameter in at least one dimension, for CLL ≥ 5000 leukemia cells/mm3, for WM presence of immunoglobulin M paraprotein with a minimum IgM level ≥ 1000 mg/dL and infiltration of bone marrow by lymphoplasmacytic cells), and pre-identified DLBCL ABC subtype by immunohistochemistry (IHC).
  • 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), except for CLL patients. Salvage therapy/conditioning regimen leading up to autologous bone marrow transplantation is considered to be one regimen (This inclusion criterion does not apply to the DLBCL-ABC cohort).
  • 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 (unless patients have CLL and bone-marrow involvement, provided they are not transfusion-dependent)
    • Absolute neutrophil count (ANC) < 1500/µL (unless patients have CLL and bone-marrow involvement)
    • Hgb < 8.0 g/dL
  • 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.
  • 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.
  • Hepatitis B sAg or Hepatitis C positive.
  • 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 < 2 years ago, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas.

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): NCT00849654

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United States, California
Stanford University School of Medicine
Palo Alto, California, United States, 94305
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
National Cancer Institute
Bethesda, Maryland, United States, 20892-1203
United States, New York
New York Prebyterian Hospital Cornell Medical Center
New York, New York, United States, 10065
United States, Oregon
Willamette Valley Cancer Institute/Research Ctr
Eugene, Oregon, United States, 97401
United States, Texas
University of Texas, MD Anderson
Houston, Texas, United States, 77030
United States, Vermont
University of Vermont College of Medicine
Burlington, Vermont, United States, 05405
United States, Washington
Northwest Cancer Specialists, Vancouver Cancer Center
Vancouver, Washington, United States, 98684
Yakima Valley Memorial Hospital/North Star Lodge Cancer Ctr
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Pharmacyclics LLC.
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Study Director: Thorsten Graef, MD, PhD Pharmacyclics LLC.
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Pharmacyclics LLC. Identifier: NCT00849654    
Obsolete Identifiers: NCT01177878
Other Study ID Numbers: PCYC-04753
First Posted: February 24, 2009    Key Record Dates
Last Update Posted: May 22, 2013
Last Verified: May 2013
Keywords provided by Pharmacyclics LLC.:
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:
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Lymphoma, B-Cell
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid