Clinical trial NCT02381080: Interaction Study of Ibrutinib and Cytochrome P450 (CYP) 3A Inhibitors in Participants With B-cell Malignancy
Official title: A Drug-drug Interaction Study of Ibrutinib With Moderate and Strong CYP3A Inhibitors in Patients With B-cell Malignancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-Cell Chronic Lymphocytic Leukemia
Keywords: B-Cell Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Marginal Zone Lymphoma
Mantle Cell Lymphoma
Follicular Lymphoma
Waldenstrom's Macroglobulinemia
Ibrutinib
IMBRUVICA
PCI-32765
JNJ-54179060
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-03-06
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility 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)

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
timeFrame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
measure: Minimum Observed Plasma Concentration (Cmin) of Ibrutinib
timeFrame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
timeFrame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Ibrutinib
timeFrame: Cycle 1: 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
measure: Metabolite to Parent (M/P) Ratio of Ibrutinib
timeFrame: Cycle 1: 0 hour (hr) pre-dose on Day 1; 0 hr pre-dose, 0.5,1,2,3,4,6,8 and 24 hrs post-dose on Day 4, 11, 18, and 25
Secondary outcomes:
measure: Partial Area Under the Plasma Concentration-Time Curve Between 2 Defined Timepoints (AUC [t1 and t2]) of Voriconazole
timeFrame: Cycle 1: 0 hour (hr) pre-dose on Day 5; 0 hr pre-dose, 0.5,1,2,3,4,6 and 24 hrs post-dose on Day 18 and 25
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Screening up to end of study (up to 8 months)
Other outcomes:
Locations:
city: N/a N/a
country: Canada
city: Moscow
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Madrid
country: Spain
city: Pamplona
country: Spain
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trials
role: STUDY_DIRECTOR
References: