Diffuse Large Cell B-lymphoma Clinical Trial
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)
The purpose of this study is to evaluate the efficacy of PCI-32765 in relapsed/refractory de novo activated B-cell (ABC) and germinal-cell B-Cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL).
| Status | Completed |
| Enrollment | 78 |
| Est. completion date | October 2014 |
| Est. primary completion date | October 2014 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | National Cancer Institute | Bethesda | Maryland |
| United States | The Ohio Sate university | Columbus | Ohio |
| United States | Hackensack University Medical Center | Hackensack | New Jersey |
| United States | The University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | UCLA Medical Center | Los Angeles | California |
| United States | University of Wisconsin | Madison | Wisconsin |
| United States | Long Island Jewish Medical Center | New Hyde Park | New York |
| United States | Memorial Sloan-Kettering Cancer Center | New York | 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 | University of Nebraska Medical Center | Omaha | Nebraska |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | University of Rochester School of Medicine and Dentistry | Rochester | New York |
| United States | Univerity of Washington | Seattle | Washington |
| United States | Stanford University School of Medicine | Stanford | California |
| Lead Sponsor | Collaborator |
|---|---|
| Pharmacyclics |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | To measure the number of patients with a response to study drug | Participants will be followed until progression of disease or start of another anti-cancer treatment. | 24 weeks from first dose | No |
| Secondary | To measure the number of patients with adverse events as a measure of safety and tolerability. | Participants will be followed until progression of the disease or start of another anticancer treatment. | For 30 days after the last dose of PCI-32765 | Yes |
| Secondary | To measure the number of participants pharmacokinetics to assist in determining how the body responses to the study drug. | Procedure will be performed during the first month of receiving study drug. | Yes |