Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

NCT ID: NCT01325701

Last Updated: 2017-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2014-10-31

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.

Conditions

Diffuse Large Cell B-lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PCI-32765: 560 mg

Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.

Group Type: EXPERIMENTAL

ibrutinib

Intervention Type: DRUG

ibrutinib is an inhibitor of BTK

PCI-32765: 840 mg

Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.

Group Type: EXPERIMENTAL

ibrutinib

Intervention Type: DRUG

ibrutinib is an inhibitor of BTK

Interventions

ibrutinib

ibrutinib is an inhibitor of BTK

Intervention Type: DRUG

Other Intervention Names

PCI-32765, Imbruvica

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darrin Beaupre, MD

Role: STUDY_DIRECTOR

Pharmacyclics LLC.

Locations

UCLA Medical Center

Los Angeles, California, United States

Stanford University School of Medicine

Stanford, California, United States

National Cancer Institute

Bethesda, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

New York University

New York, New York, United States

Weill Medical College of Cornell University

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of Rochester School of Medicine and Dentistry

Rochester, New York, United States

The Ohio Sate university

Columbus, Ohio, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Univerity of Washington

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26193343 (View on PubMed)

Other Identifiers

PCI-32765

Identifier Type: OTHER

Identifier Source: secondary_id

PCYC-1106-CA

Identifier Type: -

Identifier Source: org_study_id