NCT00849654

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
66

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Feb 2009

Typical duration for phase_1

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2009

Completed
19 days until next milestone

First Submitted

Initial submission to the registry

February 20, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 24, 2009

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2012

Completed
Last Updated

May 22, 2013

Status Verified

May 1, 2013

Enrollment Period

3.4 years

First QC Date

February 20, 2009

Last Update Submit

May 21, 2013

Conditions

B-Cell LymphomaB-Cell Leukemia

Keywords

PCI-32765LymphomaLymphoma, Non-HodgkinLymphoma, B-CellBurkitt LymphomaLymphoma, B-Cell, Marginal ZoneLymphoma, B-Cell, DiffuseLymphoma, FollicularLymphoma, Mantle CellLeukemia, LymphoidLeukemia, B-CellWaldenstrom macroglobulinemiaBruton's Tyrosine Kinase

Outcome Measures

Primary Outcomes (3)

  • Dose limiting toxicity assessment for each patient.

    At the end of the first 35 day cycle

  • Adverse events

    30 days after last dose of study drug

  • Pharmacokinetic/ Pharmacodynamic assessments

    during Cycle 1

Secondary Outcomes (1)

  • Tumor response

    at the end of Cycles 2, 4, and 6 unitl progression

Study Arms (1)

PCI-32765

EXPERIMENTAL
Drug: PCI-32765

Interventions

PCI-32765DRUG

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.

PCI-32765

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Stanford University School of Medicine

Palo Alto, California, 94305, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892-1203, United States

Location

New York Prebyterian Hospital Cornell Medical Center

New York, New York, 10065, United States

Location

Willamette Valley Cancer Institute/Research Ctr

Eugene, Oregon, 97401, United States

Location

University of Texas, MD Anderson

Houston, Texas, 77030, United States

Location

University of Vermont College of Medicine

Burlington, Vermont, 05405, United States

Location

Northwest Cancer Specialists, Vancouver Cancer Center

Vancouver, Washington, 98684, United States

Location

Yakima Valley Memorial Hospital/North Star Lodge Cancer Ctr

Yakima, Washington, 98902, United States

Location

Related Publications (3)

  • Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. doi: 10.1038/nm.3884. Epub 2015 Jul 20.

    PMID: 26193343DERIVED

  • Marostica E, Sukbuntherng J, Loury D, de Jong J, de Trixhe XW, Vermeulen A, De Nicolao G, O'Brien S, Byrd JC, Advani R, McGreivy J, Poggesi I. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015 Jan;75(1):111-21. doi: 10.1007/s00280-014-2617-3. Epub 2014 Nov 8.

    PMID: 25381051DERIVED

  • Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013 Jan 1;31(1):88-94. doi: 10.1200/JCO.2012.42.7906. Epub 2012 Oct 8.

    PMID: 23045577DERIVED

Related Links

MeSH Terms

Conditions

Lymphoma, B-CellLeukemia, B-CellLymphomaLymphoma, Non-HodgkinBurkitt LymphomaLymphoma, B-Cell, Marginal ZoneLymphoma, FollicularLymphoma, Mantle-CellLeukemia, LymphoidWaldenstrom Macroglobulinemia

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemiaHematologic DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Study Officials

  • Thorsten Graef, MD, PhD

    Pharmacyclics LLC.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 20, 2009

First Posted

February 24, 2009

Study Start

February 1, 2009

Primary Completion

July 1, 2012

Study Completion

July 1, 2012

Last Updated

May 22, 2013

Record last verified: 2013-05

Locations

US(9)