A Study Of PF-04449913 In Select Hematologic Malignancies

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade (1 = mild AE, 2 = moderate AE, 3 = severe AE, 4 = life-threatening or disabling AE, 5 = death related to AE) was reported.

An AE was any untoward medical occurrence in a participant. Treatment-related AEs are events that were assessed by the investigator as related to study medication. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade (1 = mild AE, 2 = moderate AE, 3 = severe AE, 4 = life-threatening or disabling AE, 5 = death related to AE) was reported.

Participants with systolic blood pressure (BP) less than (<) 90 millimeters of mercury (mmHg), maximum increase and decrease from baseline systolic BP of more than or equal to (>=) 30 mmHg, diastolic BP <50 mmHg, maximum increase and decrease from baseline diastolic BP >=20 mmHg, and a heart rate of more than (>) 120 beats per minute (bpm) at any time post dose were summarized.

Number of participants with laboratory test abnormalities without regard to baseline abnormality as per the pre defined criteria were reported. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).

Ribonucleic acid (RNA) was extracted from skin samples and complementary deoxyribonucleic acid (cDNA) was prepared. Gene expression was measured using custom Taqman low density array (TLDA) cards run on the Applied Biosystems ViiATM 7 system.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Accumulation ratio was calculated as AUCtau at steady state (Cycle 1/Day 21)/AUCtau on Cycle 1 Day 1.

Linearity ratio was calculated as AUCtau at steady state (Cycle 1/Day 21)/AUCinf after single dose (Lead-in Period [Day -6]).

Renal clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by the kidneys.

Percentage of participants with OR based on assessment of disease response according to disease specific response criteria (hematologic, cytogenetic and molecular responses). Results were analyzed based on malignancies, according to the planned analysis.

Time in months from start of study treatment to first documentation of objective disease progression or death due to cancer, whichever comes first. TTP was calculated as (first event date - date of first dose of study medication + 1)/30.4. Disease progression was determined from oncologic assessment data (where data met the criteria for disease progression: categorized as early progressor from chronic phase [CP], progressor to accelerated phase [AP] or blast crisis [BC] from CP or return to CP, progressor to AP to BC, loss of confirmed complete hematologic response, or loss of major cytogenetic response).

Time in months from the first documentation of objective response to objective disease progression or death due to any cancer. DR was calculated as [date of first documentation of progression or death due to cancer - date of first disease response + 1]/30.4. DR was calculated for the subgroup of participants with an objective disease response.

Time in months from start of study treatment to first documentation of objective disease progression or death due to any cause. PFS was calculated as [first event date - date of first dose of study medication + 1]/30.4. Disease progression was determined from oncologic assessment data (where data met the criteria for disease progression: categorized as early progressor from CP, progressor to AP or BC from CP or return to CP, progressor to AP to BC, loss of confirmed complete hematologic response, or loss of major cytogenetic response; or from adverse event data (where the outcome was "Death").

Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. The time from ECG Q wave to the end of the T wave corresponding to electrical systole (QT) was corrected for heart rate (QTc). QTc using Fridericia's formula (QTcF) was calculated. Participants with maximum increase from baseline of <30 millisecond (msec), 30 to <60 msec and >=60 msec were summarized.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. QTcF was calculated. Participants with maximum decrease from baseline of <30 msec, 30 to <60 msec and >=60 msec were summarized.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. QTcF was calculated. Participants with post-baseline absolute QTcF values >=500 msec were summarized.