t of Fertility
Carcinogenicity studies have not been conducted with ibrutinib.
Ibrutinib was not mutagenic in a bacterial mutagenicity (Ames) assay, was not clastogenic in a chromosome aberration assay in mammalian (CHO) cells, nor was it clastogenic in an in vivo bone marrow micronucleus assay in mice at doses up to 2000 mg/kg.
Fertility studies with ibrutinib have not been conducted in animals. In the general toxicology studies conducted in rats and dogs, orally administered ibrutinib did not result in adverse effects on reproductive organs.
14 CLINICAL STUDIES
14.1 Mantle Cell Lymphoma
The safety and efficacy of IMBRUVICA in patients with MCL who have received at least one prior therapy were eva luated in an open-label, multi-center, single-arm trial of 111 previously treated patients. The median age was 68 years (range, 40 to 84 years), 77% were male, and 92% were Caucasian. At baseline, 89% of patients had a baseline ECOG performance status of 0 or 1. The median time since diagnosis was 42 months, and median number of prior treatments was 3 (range, 1 to 5 treatments), including 11% with prior stem cell transplant. At baseline, 39% of subjects had at least one tumor ≥ 5 cm, 49% had bone marrow involvement, and 54% had extranodal involvement at screening.
IMBRUVICA was administered orally at 560 mg once daily until disease progression or unacceptable toxicity. Tumor response was assessed according to the revised International Working Group (IWG) for non-Hodgkin's lymphoma (NHL) criteria. The primary endpoint in this study was investigator-assessed overall response rate (ORR). Responses to IMBRUVICA are shown in Table 3.
Table 3: Overall Response Rate (ORR) and Duration of Response (DOR) Based on Investigator Assessment in Patients with Mantle Cell Lymphoma Total (N=111)
CI = confidence interval; CR = complete response; PR = partial response; NR = not reached
ORR (%) 65.8
95% CI (%) (56.2, 74.5)
CR (%) 17.1
PR (%) 48.6
Median DOR months 95% CI 17.5 (15.8, NR)
An Independent Review Committee (IRC) performed independent reading and interpretation of imaging scans. The IRC review demonstrated an ORR of 69%.
The median time to response was 1.9 months.
Lymphocytosis
Upon initiation of IMBRUVICA, a temporary increase in lymphocyte counts (i.e., ≥ 50% increase from baseline and above absolute lymphocyte count of 5,000/mcL) occurred in 33% of patients in the MCL study. The onset of isolated lymphocytosis occurs during the first few weeks (median time 1.1 weeks) of IMBRUVICA therapy and resolves by a median of 8 weeks.
16 HOW SUPPLIED/STORAGE AND HANDLING
The white opaque 140 mg capsules marked with "ibr 140 mg" in black ink are available in white HDPE bottles with a child-resistant closure:
90 capsules per bottle: NDC 57962-140-09
120 capsules per bottle: NDC 57962-140-12
Store bottles at room temperature 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F to 86°F). Retain in original package.
17 PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Patient Information)
Hemorrhage:
Inform patients of the possibility of bleeding, and to report any signs or symptoms (blood in stools or urine, prolonged or uncontrolled bleeding). Inform the patient that IMBRUVICA may need to be interrupted for medical or dental procedures [see Warnings and Precautions (5.1)].
Infections:
Inform patients of the possibil |
