Primary Outcomes

Description: Best clinical response was defined as complete response (CR) or partial response (PR), according to NCI definitions for AML and the guidelines for defining responses in MDS.

Measure: Number of Participants With Best Clinical Response (Core)

Time: from date of first patient first visit (FPFV), 29-Jan-2002, to date of last participant last visit (LPLV), 04-Sep-2003

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Measure: Percent Decrease in Phospho-FLT3 Compared to Baseline (Core)

Time: days 1, 28

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Description: Overall clinical response was defined as CR, PR, minor response (MR) or blast response (BR). CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.

Measure: Number of Participants With Overall Clinical Response (E1)

Time: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004

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Measure: Percent Decrease in Phospho-FLT3 Compared to Baseline (E1)

Time: days 1, 28

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Measure: Percent Decrease in Phospho-FLT3 Compared to Baseline (E2)

Time: Days 1, 28

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Description: Blood samples were collected for pharmacokinetic (PK) analysis.

Measure: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for PKC412 Plasma in the PKC + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for pharmacokinetic (PK) analysis.

Measure: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for PKC412 in the PKC + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for PK analysis.

Measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for PK analysis.

Measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for PK analysis.

Measure: Terminal Elimination Half-life (T1/2) for PKC412 in the PKC + Itrconazole Combination Arm (E2)

Time: Cycle 1: days 21 and 22

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Description: Blood samples were collected for pharmacokinetic (PK) analysis.

Measure: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP62221 Plasma in the PKC + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for pharmacokinetic (PK) analysis.

Measure: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP62221 in the PKC + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for PK analysis.

Measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP62221 in the PKC412 + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for PK analysis.

Measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP622221 in the PKC412 + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for PK analysis.

Measure: Terminal Elimination Half-life (T1/2) for CGP62221 in the PKC + Itrconazole Combination Arm (E2)

Time: Cycle 1: day 22,

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Description: Blood samples were collected for pharmacokinetic (PK) analysis.

Measure: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP52421 Plasma in the PKC + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for pharmacokinetic (PK) analysis.

Measure: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP52421 in the PKC + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for PK analysis.

Measure: Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for PK analysis.

Measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)

Time: Cycle 1: days 21, 22, 28

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Description: Blood samples were collected for analysis.

Measure: Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)

Time: Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15

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Description: Blood samples were collected for analysis.

Measure: Summary of CGP62221 Concentration (E2)

Time: Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15

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Description: Blood samples were collected for analysis.

Measure: Summary of CGP52421 Concentration (E2)

Time: Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15

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Secondary Outcomes

Description: TTP was defined as the time from first dose date to date of disease progression which is identified as study completion date for unsatisfactory treatment effect or date of death from any cause within the 28 day cutoff post treatment.

Measure: Time to Disease Progression (TTP) (Core)

Time: from date of FPFV, 29-Jan-2002, to date of LPLV, 04-Sep-2003

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Description: Blood samples were collected for analysis.

Measure: Summary of Midostaurin Plasma Concentration (Core)

Time: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,

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Description: Blood samples were collected for analysis.

Measure: Summary of CGP62221 Plasma Concentration (Core)

Time: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,

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Description: Blood samples were collected for analysis.

Measure: Summary of CGP52421 Plasma Concentration (Core)

Time: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,

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Description: TTP was defined as the time from the first dose date to the date of disease progression (defined as the study completion date for unsatisfactory treatment effect, date of response assessment of progressive disease, or date of death from any cause). One participant from the wild type 200 mg group did not have any assessment on treatment and therefore was not taken into account for TTP.

Measure: Time to Disease Progression (E1)

Time: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004

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Description: OS was measured from the date of the first dose of treatment to the date of death from any cause or to the last date that the patient was known to be alive (a censored observation).

Measure: Overall Survival (OS) (E1)

Time: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004

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Description: Duration of best clinical response was measured from the time that the measurement criteria were met for CR, PR, MR (with or without blast reduction) or BR until the first date that recurrent disease was documented (event) or until the date of last follow up.

Measure: Duration of Best Clinical Response (E1)

Time: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004

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Description: Event-free survival was defined as the time from date of start of treatment to the date of death from any cause, treatment failure or relapse

Measure: Event-free Survival (E1)

Time: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004

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Description: Blood samples were collected for analysis.

Measure: Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)

Time: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)

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Description: Blood samples were collected for analysis.

Measure: Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)

Time: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)

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Description: Blood samples were collected for analysis.

Measure: Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)

Time: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)

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Description: Blood samples were collected for analysis.

Measure: Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)

Time: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)

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Description: Blood samples were collected for analysis.

Measure: Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)

Time: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)

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Description: Blood samples were collected for analysis.

Measure: Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)

Time: Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)

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Description: Best clinical response was defined as CR, PR, MR, MR+BR, or BR . CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.

Measure: Best Clinical Response (E2)

Time: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008

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Description: TTP was defined as the time from the first dose date to the date of disease progression, which was defined as the study completion date for unsatisfactory treatment effect, the date of response assessment of progressive disease, or the date of death from any cause

Measure: Time to Disease Progression (E2)

Time: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008

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Description: OS was measured from the date of the first dose of treatment to the date of death from any cause or the last date the patient was known to be alive (censored observation)

Measure: Overall Survival (E2)

Time: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008

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