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

Pharmacyclics

Status and phase: Completed; Phase 2

Conditions: Diffuse Large Cell B-lymphoma

Treatments: Drug: ibrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01325701

PCYC-1106-CA

PCI-32765 (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 78 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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78 participants in 2 patient groups

PCI-32765: 560 mg

Experimental group

Description:

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

Treatment:

Drug: ibrutinib

PCI-32765: 840 mg

Experimental group

Description:

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

Treatment:

Drug: ibrutinib