Oral Enzastaurin in Participants With Relapsed Mantle Cell Lymphoma

Using the Standardized Response Criteria for non-Hodgkin's lymphomas, participants were considered to have progressive disease if there was a 50% increase in the sum of the products of the greatest diameters (SPD) of the dominant nodal and non-nodal sites or appearance of new-involved site or lesion. The percentage of FFP was computed as the number of participants documented to be progression free after 3 cycles of treatment divided by the number of treated participants and then multiplied by 100.

Time frame: Baseline through at least 3 cycles of treatment (28-day cycle)

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug.

The Steady-state plasma concentrations of total analytes (enzastaurin plus its active metabolite, LSN326020) observed after once-daily dosing were evaluated using sparse sampling methodology.

Time frame: Cycles 1 [1-4 hours (h) and 4-8 h postdose], 2 (predose, 2-4 h and 6-8 h postdose), and 3 (predose and 2-8 h postdose) of Day 1 of each 28-day cycle

Population: All enrolled participants who received at least 1 dose of study drug and had evaluable data for Cav,ss.

Overall health status and participant utility values were measured with the EuroQol-5D questionnaire. EuroQol-5D describes health status in terms of 5 dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension is divided into 3 levels: 1 (no problem), 2 (some problem), and 3 (extreme problem). The questionnaire records the level of problems on each of 5 dimensions and is converted into the EuroQol-5D index based on preference weights (Dolan 1997), where a score of 0.0 = death and 1.0 = perfect health.

Time frame: Baseline, Cycles 2, 4 and 6

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug and had EuroQol-5D assessed at baseline and Cycles 2, 4, and 6.

The B symptoms, tumor-related symptoms, participant functioning, and health-related quality of life were assessed with FACT-Lym v. 4. FACT-Lym v. 4 consists of 42 items with 5-point rating scales for each item, where 0 = not at all and 4 = very much. Physical well-being, social/family well-being and functional well-being subscales consist of 7 items each with scores ranging from 0-28. The emotional well-being subscale consists of 6 items with a score ranging from 0-24. The lymphoma tumor - specific subscale consists of 15 items with a score ranging from 0-60. Fact-Lymphoma total score ranges from 0-168. A higher score represents better quality of life.

Time frame: Baseline, Cycles 2, 4 and 6 (28-day cycle)

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug and had FACT-Lym assessed at baseline and Cycles 2, 4 and 6.

Duration of overall response for responders was measured from the date that measurement criteria were met for CR, CRu, PR or SD (whichever status occurred first) until the first date of documented progressive disease or death due to any cause, whichever occurred first. Using the Standardized Response Criteria for non-Hodgkin's lymphomas Guidelines, CR was defined as the disappearance of all lesions. CRu was the disappearance of clinical and radiographic evidence of disease, normal appearance of spleen and greater than 75% regression in lymph node mass. PR was defined as at least a 50% decrease in the six largest dominant nodes. SD was when the response was poorer than partial response with no new lesions consistent with progressive disease. Duration of response was censored at the date of the last assessment visit for responders who were still alive and had not had documented progressive disease.

Time frame: Date of progression or death due to any cause up to 22.01 months

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug and met criteria for CR, CRu, PR or SD. Participants censored = 2.

Data presented are the number of participants who experienced SAEs, AEs, deaths due to progressive disease (PD), and deaths due to AEs while on treatment and death during the 30-day post-treatment follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Time frame: Each cycle (28-day cycle) up to 21 cycles and 30-day follow-up

Population: All enrolled participants who received at least 1 dose of study drug.

IHC staining of tumor samples was carried out to determine Ki-67 expression. High expression is defined as the percentage of positive cells ≥40%.

Time frame: Baseline

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug and provided tissue specimens from the initial diagnosis for Ki-67 expression analysis.

IHC staining of tumor samples was carried out to determine PKCβ expression. Staining intensity was measured on a semiquantitative scale of 0 (or negative) to 3 (high intensity). The final score combined the components of staining intensity and the percentage of positive cells and was defined as \[1 \* (percentage of cells staining at 1)\] + \[2 \* (percentage of cells staining at 2)\] + \[3 \* (percentage of cells staining at 3)\]. Score ≥100 and staining intensity ≥2 indicates high expression for PKCβ, while score \<100 and staining intensity ≤1 indicates low expression for PKCβ.

Time frame: Baseline

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug and provided tissue specimens from the initial diagnosis for PKCβ expression analysis.

OS was defined as the time from the date of enrollment to the date of death due to any cause. For each participant who was not known to have died as of the data-inclusion cut-off date, OS was censored for that analysis at the date of the last assessment visit prior to the cut-off date.

Time frame: Baseline to date of death from any cause at least up to 23.10 months

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug. Participants censored = 39.

Time frame: Baseline to 22.01 months

Population: Zero participants were analyzed as no participant achieved CR, CRu or PR.

PFS time was defined as the time from the date of enrollment to the first date of documented progressive disease or death due to any cause, whichever occurred first. Using the Standardized Response Criteria for non-Hodgkin's lymphomas, participants were considered to have progressive disease if there was a 50% increase in the sum of the products of the greatest diameters (SPD) of the dominant nodal and non-nodal sites or appearance of new-involved site or lesion. Progression-free survival time was censored at the date of the last assessment visit for participants who were still alive and who had not had documented progressive disease.

Time frame: Baseline to measured progressive disease or death due to any cause up to 22.01 months

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug. Participants censored = 3.

Time to new treatment was as the time from enrollment to the date new treatment for the cancer under study was initiated. Time to new treatment was censored at the date of the last assessment visit for participants who were not documented to have initiated a new treatment.

Time frame: Baseline to date of new treatment up to 23.10 months

Population: All enrolled participants with relapsed mantle cell lymphoma who received at least 1 dose of study drug. Participants censored =16.