Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

February 20, 2009
May 21, 2013
February 2009
July 2012   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT00849654 on ClinicalTrials.gov Archive Site
Tumor response [ Time Frame: at the end of Cycles 2, 4, and 6 unitl progression ] [ Designated as safety issue: No ]
Tumor response [ Time Frame: at the end of Cycles 2, 4, and 6 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of the Safety and Tolerability of PCI-32765 in Patients With Recurrent B Cell Lymphoma
Phase I Dose-Escalation Study of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Recurrent B Cell Lymphoma

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • B-Cell Lymphoma
  • B-Cell Leukemia
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.

Experimental: PCI-32765
Intervention: Drug: PCI-32765
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
66
July 2012
July 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00849654
PCYC-04753
No
Pharmacyclics
Pharmacyclics
Not Provided
Study Director: Thorsten Graef, MD, PhD Pharmacyclics
Pharmacyclics
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP