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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT00849654
First received: February 20, 2009
Last updated: May 21, 2013
Last verified: May 2013
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 unitl progression ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: February 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  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 (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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00849654

Locations
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
Investigators
Study Director: Thorsten Graef, MD, PhD Pharmacyclics
  More Information

Additional Information:
No publications provided by Pharmacyclics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT00849654     History of Changes
Obsolete Identifiers: NCT01177878
Other Study ID Numbers: PCYC-04753
Study First Received: February 20, 2009
Last Updated: May 21, 2013
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:
Lymphoma, B-Cell
Lymphoma
Leukemia
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid

ClinicalTrials.gov processed this record on October 16, 2014