Safety and Efficacy Study of Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01325701
First received: February 2, 2011
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the efficacy of PCI-32765 in relapsed/refractory de novo activated B-cell (ABC) and germinal-cell B-Cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL).


Condition Intervention Phase
Diffuse Large Cell B-lymphoma
Drug: PCI-32765
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Phase 2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Refractory or de Novo Diffuse Large B-cell Lymphoma (DLBCL)

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • To measure the number of patients with a response to study drug [ Time Frame: 24 weeks from first dose ] [ Designated as safety issue: No ]
    Participants will be followed until progression of disease or start of another anti-cancer treatment.


Secondary Outcome Measures:
  • To measure the number of patients with adverse events as a measure of safety and tolerability. [ Time Frame: For 30 days after the last dose of PCI-32765 ] [ Designated as safety issue: Yes ]
    Participants will be followed until progression of the disease or start of another anticancer treatment.

  • To measure the number of participants pharmacokinetics to assist in determining how the body responses to the study drug. [ Time Frame: Procedure will be performed during the first month of receiving study drug. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 125
Study Start Date: May 2011
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PCI-32765 (Treatment Group 1)
560 mg/daily
Drug: PCI-32765
Experimental: PCI-32765 (Treatment Group 2)
840 mg/daily
Drug: PCI-32765

  Eligibility

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

Inclusion Criteria:

  1. Men and women ≥ 18 years of age.
  2. ECOG performance status ≤ 2.
  3. Pathologically confirmed de novo DLBCL
  4. Subjects must have available tissue for central pathology review to be eligible. Treatment Group 2: Subjects will be eligible if they have the non-GCB phenotype, as confirmed by Central IHC testing by the Hans method.
  5. Relapsed or refractory disease, defined as either: 1) recurrence of disease after a CR, or 2) PR, SD, or progressive disease (PD) at completion of the treatment regimen preceding entry to the study (residual disease): Subjects must have previously received an appropriate first-line treatment regimen. Subjects who have not received HDT/ASCT must be ineligible for HDT/ASCT
  6. Treatment Group 1: Subjects must have ≥ 1 measurable (> 2 cm in longest dimension) disease sites on CT scan. Treatment Group 2: Subjects must have ≥ 1 measurable (> 1.5 cm in longest dimension) disease sites on CT scan.

Exclusion Criteria:

  1. Transformed DLBCL or DLBCL with coexistent histologies (eg, FL or MALT).
  2. Primary mediastinal (thymic) large B-cell lymphoma.
  3. Known central nervous system lymphoma. In addition, for subjects in Treatment Group 2, known leptomeningeal involvement is exclusionary.
  4. Certain exclusions on prior therapy
  5. Major surgery within 2 weeks of first dose of study drug.
  6. Any of the following laboratory abnormalities:

    1. ANC < 0.75 x 10^9/L. Treatment Group 2: Eligible subjects must be independent of growth factor support for 7 days prior to the screening lab tests.
    2. Platelet count < 50 x 10^9/L independent of transfusion support. Treatment Group 2 only: Eligible subjects must be independent of transfusion support for 7 days prior to the screening lab tests.
    3. AST or ALT ≥ 3.0 x upper limit of normal (ULN)
    4. Creatinine > 2.0 x ULN
    5. Treatment Group 2 only: Hemoglobin < 8.0 g/dL
    6. Treatment Group 2 only: Total Bilirubin > 1.5 x ULN
  7. Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon)
  8. Treatment Group 2: Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
  9. Treatment Group 2: Known bleeding diathesis, eg, von Willebrand's disease, hemophilia.
  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: NCT01325701

Locations
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Maryland
National Cancer Institute
Bethesda, Maryland, United States, 20892-1203
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11042
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Weill Medical College of Cornell University
New York, New York, United States, 10021
New York University
New York, New York, United States, 10016
University of Rochester School of Medicine and Dentistry
Rochester, New York, United States, 14642
United States, Ohio
The Ohio Sate university
Columbus, Ohio, United States, 43210
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Univerity of Washington
Seattle, Washington, United States, 98109
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
Pharmacyclics
Investigators
Study Director: Darrin Beaupre, MD Pharmacyclics
  More Information

No publications provided

Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01325701     History of Changes
Other Study ID Numbers: PCYC-1106-CA, PCI-32765
Study First Received: February 2, 2011
Last Updated: March 7, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Pharmacyclics:
PCI-32765
Lymphoma, B-Cell
Bruton's Tyrosine Kinase
Non Hodgkin's Lymphoma
Germinal Center B-Cell
Activated B-Cell

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on July 23, 2014