Interaction Study of Ibrutinib and Cytochrome P450 (CYP) 3A Inhibitors in Participants With B-cell Malignancy

Condition(s) targeted: B-Cell Chronic Lymphocytic Leukemia

Intervention: Ibrutinib (Drug); Erythromycin (Drug); Voriconazole (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Janssen Research & Development, LLC

Official(s) and/or principal investigator(s):
Janssen Research & Development, LLC Clinical Trials, Study Director, Affiliation: Janssen Research & Development, LLC

Overall contact:
Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: JNJ.CT@sylogent.com

The purpose of this study is to assess the effect of a moderate Cytochrome P450 (CYP) 3A inhibitor (erythromycin) and a strong CYP3A inhibitor (voriconazole) on the steady-state pharmacokinetics (PK [the study of the way a drug enters and leaves the blood and tissues over time]) of repeated oral doses of ibrutinib in participants with B-cell malignancy (cancer or other progressively enlarging and spreading tumors).

Official title: A Drug-drug Interaction Study of Ibrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-cell Malignancy

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Minimum Observed Plasma Concentration (Cmin) of Ibrutinib

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib

Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Ibrutinib

Metabolite to Parent (M/P) Ratio of Ibrutinib

Secondary outcome:

Partial Area Under the Plasma Concentration-Time Curve Between 2 Defined Timepoints (AUC [t1 and t2]) of Voriconazole

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Detailed description: This is an open-label (participants and researchers are aware about the treatment participants are receiving), multi-center (when more than 1 hospital or medical school team work on a medical research study), drug-drug interaction (DDI) study of ibrutinib with the moderate and the strong CYP3A inhibitors (erythromycin and voriconazole respectively) in participants with B-cell malignancies (including Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma [CLL/SLL], Follicular Lymphoma [FL], Marginal Zone Lymphoma [MZL], Waldenstrom's Macroglobulinemia [WM] or Mantle Cell Lymphoma [MCL]). The study will consist of a Screening Phase (28 days), a Treatment Phase (consisting of six 28-days cycles), and an End-of-Treatment (EoT) Visit (within 30 days after the last dose of study drug). The study will consist of 2 Parts. In Part 1, extent of the DDI between ibrutinib at dose level of 140 milligram (mg) and CYP3A inhibitors will be assessed. After completion of Part 1 of the study, an interim analysis of all available PK and safety data will be conducted and Part 2 will only be performed if the observed drug interaction is less than anticipated based on current information. In Part 2, safety and PK of ibrutinib at dose level of 560 mg administered with CYP3A inhibitors will be assessed. Participants who continue to derive clinical benefit from ibrutinib treatment at the end of this study, and who are eligible to continue in the PCI-32765CAN3001 study (NCT01804686) will end their participation in this trial, have an EoT visit completed, and will continue receiving ibrutinib as a part of the PCI-32765CAN3001 protocol. Participants' safety will be monitored throughout the study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Histologically or cytologically confirmed Chronic Lymphocytic Leukemia /Small

Lymphocytic Lymphoma (CLL/SLL), Marginal Zone Lymphoma (MZL), Mantle Cell Lymphoma (MCL), Follicular Lymphoma (FL), or Waldenstrom's Macroglobulinemia (WM)

- Relapsed or refractory disease after at least 1 prior line of systemic therapy

(participants with FL or MZL must have failed anti-CD20 monoclonal antibody containing chemotherapy regimen)

- Eastern Cooperative Oncology Group Performance Status score of 0 or 1

- Hematology values within the following limits: a) Absolute neutrophil count (ANC)

greater than and equal to (>=) 1. 0*10^9 per liter (L); b) Platelets >=50*10^9/L without transfusion support within 7 days; c) Hemoglobin >=8 gram per deciliter (g/dL) without transfusion support within 7 days; d) Prothrombin time /International normalized ratio (PT/INR) less than equal to (<=) 1. 5*Upper Limit of Normal (ULN) and activated partial thromboplastin time (aPTT) <=1. 5*ULN

- Biochemical values within the following limits: a) Alanine aminotransferase (ALT) and

aspartate aminotransferase (AST) <=3. 0*ULN; b) Total bilirubin <=1. 5*ULN (unless due to Gilbert's syndrome); c) Serum creatinine <=1. 5*ULN or a calculated creatinine clearance of >=50 milliliter per minute per 1. 73 square meter Exclusion Criteria:

- Major surgery within 4 weeks of the first dose of ibrutinib

- Diagnosed or treated for malignancy other than the indication under study except for:

a) Adequately treated non-melanoma skin cancer or lentigo maligna, curatively treated in-situ cancer without evidence of disease; b) Malignancy treated with curative intent and with no known active disease present for >=3 years before the first dose of ibrutinib

- History of stroke or intracranial hemorrhage within 6 months prior to the first dose

of ibrutinib

- History of galactose intolerance

- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (for

example, phenprocoumon)

Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: JNJ.CT@sylogent.com

N/a N/a, Canada; Recruiting

Moscow, Russian Federation; Recruiting

Petrozavodsk, Russian Federation; Recruiting

St. Petersburg, Russian Federation; Recruiting

Madrid, Spain; Recruiting

Pamplona, Spain; Recruiting

Hackensack, New Jersey, United States; Recruiting

New Brunswick, New Jersey, United States; Withdrawn

Nashville, Tennessee, United States; Withdrawn

To learn how to participate in this trial please click here.

Starting date: May 2015
Last updated: August 14, 2015