Clinical trial NCT01325701: Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large Cell B-lymphoma
Keywords: PCI-32765
Lymphoma, B-Cell
Bruton's Tyrosine Kinase
Non Hodgkin's Lymphoma
Germinal Center B-Cell
Activated B-Cell
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2011-03-30
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: The primary objectives of this study were to evaluate the efficacy of ibrutinib administered at 560 mg once per day in relapsed or refractory de novo ABC and GCB DLBCL, and to evaluate the efficacy of ibrutinib administered at 840 mg once per day in relapsed or refractory de novo ABC DLBCL.

The secondary objective was to evaluate the safety and tolerability of a fixed daily oral dosing regimen of ibrutinib in relapsed/refractory de novo DLBCL.

Eligibility 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.

Primary outcomes:
measure: Percentage of Patients With an Overall Response to Study Drug
timeFrame: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)
Secondary outcomes:
measure: Number of Patients With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years).
measure: Ibrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765
timeFrame: Performed during the first month of receiving study drug.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Bethesda
country: United States
facility: National Cancer Institute
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester School of Medicine and Dentistry
state: New York
city: Columbus
country: United States
facility: The Ohio Sate university
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Univerity of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Pharmacyclics LLC.
name: Darrin Beaupre, MD
role: STUDY_DIRECTOR
References:
citation: 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.