A Pilot Study Of Pd 0332991 In Patients With Previously Treated Mantle Cell Lymphoma

Correlation Coefficient Between Change From Baseline in Fluoro-L-thymidine Positron Emission Tomography (FLT-PET) Maximum Standard Uptake Value (SUVmax) and in Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21

时间窗: Baseline, Cycle 1 Day 21

Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram \[kg\]). Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. Change from baseline in \[(18)F\]-FLT-PET SUVmax at Cycle 1 Day 21 and change from baseline in Phospho-Rb percent positive cells at Cycle 1 Day 21 were analyzed. The change values of FLT-PET SUVmax and Phospho-Rb percent positive cells were then correlated. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Correlation Coefficient Between Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Maximum Standard Uptake Value (SUVmax) and in Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21

时间窗: Baseline, Cycle 1 Day 21

Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram \[kg\]). Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. Change from baseline in \[(18)F\]-FDG-PET SUVmax at Cycle 1 Day 21 and change from baseline in Phospho-Rb percent positive cells at Cycle 1 Day 21 were analyzed. The change values of FLT-PET SUVmax and Phospho-Rb percent positive cells were then correlated. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Change From Baseline in Maximum Standard Uptake Value (SUVmax) at Cycle 1 Day 21

时间窗: Baseline, Cycle 1 Day 21

Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram \[kg\]). Change from baseline in SUVmax was assessed using \[(18)F\]-FLT-PET and \[(18)F\]-FDG-PET techniques.

Correlation Between Positron Emission Tomography (PET) Response and Progression-Free Survival (PFS)

时间窗: Baseline, Cycle 1 Day 21 for PET response; Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) for PFS

PET response was defined as complete response (CR) = mean SUVmax same as of background; partial response (PR) = mean SUVmax less than (\<) 75 percent (%) of baseline; progressive disease (PD) = mean SUVmax greater than (\>) 125% of baseline; stable disease (SD) = mean SUVmax greater than or equal to (\>=) 75% of baseline and mean SUVmax less than or equal to (\<=) 125% of baseline. PFS was defined as the time from first dose of study medication to the first documentation of objective tumor progression, or to death due to any cause, whichever occurred first. Tumor progression was defined as \>50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease.

Correlation Between Positron Emission Tomography (PET) Response and Objective Response (OR)

时间窗: Baseline, Cycle 1 Day 21 for PET response; Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) for OR

OR: CR= disappearance of all clinical/radiographic evidence of disease, disease related symptoms and biochemical abnormalities, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeat bone marrow aspiration; PR= dominant nodes decreased by \>50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions regressed by \>50% in SPD, no new sites of disease; SD= response \<PR and no PD, documented \>=1 time after start of therapy, no new sites of disease; PD= \>50% increase in SPD of dominant nodes and other nodes or appearance of new sites of disease. PET response: CR= mean SUVmax same as background; PR= mean SUVmax \<75% of baseline; PD= mean SUVmax \>125% of baseline; SD= mean SUVmax \>=75% of baseline but \<=125% of baseline. Correlation was reported as conjoint number of participants with PET response at Cycle 1 Day 21 and OR at end of study.

Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Baseline

时间窗: Baseline

Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique.

Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21

时间窗: Cycle 1 Day 21

Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique.

Ki-67 Composite Score at Baseline

时间窗: Baseline

Percentage of Ki-67 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).

Ki-67 Composite Score at Cycle 1 Day 21

时间窗: Cycle 1 Day 21

Percentage of Ki-67 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).

Cyclin D1 Composite Score at Baseline

时间窗: Baseline

Percentage of Cyclin D1 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).

Cyclin D1 Composite Score at Cycle 1 Day 21

时间窗: Cycle 1 Day 21

Percentage of Cyclin D1 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).

Number of Participants With Laboratory Test Abnormalities

时间窗: Baseline up to 28 days after last dose of study medication

Criteria for laboratory test abnormality: Hematology (Hemoglobin \[\<0.8\*lower limit of normal {LLN}\], Platelets \[\<0.5\*LLN/ \>1.75\*upper limit of normal {ULN}\], White blood cells \[\<0.6\*LLN/ \>1.5\*ULN\], Lymphocytes, Neutrophils \[\<0.8\*LLN/ \>1.2\*ULN\], Basophils, Eosinophils, Monocytes \[\>1.2\*ULN\]); Liver Function (Total bilirubin \[\>1.5\*ULN\], Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Alkaline phosphatase \[\>0.3\*ULN\], Total protein, Albumin \[\<0.8\*LLN/ \>1.2\*ULN\]); Renal Function (Blood urea nitrogen, Creatinine \[\>1.3\*ULN\], Uric acid \[\>1.2\*ULN\]); Electrolytes (sodium \[\<0.95\*LLN/ \>1.05\*ULN\], potassium, chloride, calcium, magnesium \[\<0.9\*LLN/ \>1.1\*ULN\], phosphate \[\<0.8\*LLN/ \>1.2\*ULN\]); Other (Glucose \[\<0.6\*LLN/ \>1.5\*ULN\]).

Number of Participants With Treatment-Emergent Adverse Events by Severity

时间窗: Day 1 up to 28 days after last dose of study medication

AE = any untoward medical occurrence in participant who received study medication without regard to possibility of causal relationship. Severity was assessed as: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe) = unacceptable or intolerable events, significantly interrupting usual daily activity, and requiring systemic medication therapy/other treatment; Grade 4 (Life-threatening) = events causing participant to be in imminent danger of death; Grade 5 (Death) = death related to an AE. Treatment-emergent events = between first dose of study medication and up to 28 days after last dose, that were absent before treatment or that worsened relative to pre-treatment state. A participant may be represented in more than 1 category.

Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

时间窗: Day 1 up to 28 days after last dose of study medication

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The events which were considered treatment-related by sponsor and/or investigator were reported.