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Trial record 1 of 1 for:    NCT01546038
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A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

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ClinicalTrials.gov Identifier: NCT01546038
Recruitment Status : Active, not recruiting
First Posted : March 7, 2012
Results First Posted : May 23, 2018
Last Update Posted : May 23, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type: Interventional
Study Design: Allocation: Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Acute Myeloid Leukemia
Interventions: Drug: PF-04449913
Drug: Low dose ARA-C (LDAC)
Drug: Decitabine
Drug: Daunorubicin
Drug: Cytarabine

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Phase 1B:Unfit(unfit for intensive chemotherapy)participants with prior decitabine or azacitidine for high risk MDS or AHD(antecedent hematologic disease)were eligible for the LDAC arm only;with prior cytarabine were eligible for decitabine arm only.Phase 2:Participant's treatment arm assignment was based on the fit or unfit status at screening.

Reporting Groups
  Description
Phase 1B: Glasdegib 100 mg + LDAC Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). Low dose Ara-C (LDAC) was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Phase 1B: Glasdegib 200 mg + LDAC Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Phase 1B: Glasdegib 100 mg + Decitabine Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
Phase 1B: Glasdegib 200 mg + Decitabine Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Phase 2 Unfit: Glasdegib 100 mg + LDAC Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.
Phase 2 Unfit: LDAC Alone Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.

Participant Flow:   Overall Study
    Phase 1B: Glasdegib 100 mg + LDAC   Phase 1B: Glasdegib 200 mg + LDAC   Phase 1B: Glasdegib 100 mg + Decitabine   Phase 1B: Glasdegib 200 mg + Decitabine   Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin   Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin   Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin   Phase 2 Unfit: Glasdegib 100 mg + LDAC   Phase 2 Unfit: LDAC Alone
STARTED   17   6   4   3   16   6   71   88   44 
Received Treatment   17   6   4   3   16   6   69   84   41 
COMPLETED   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   17   6   4   3   16   6   71   88   44 
Death                15                6                4                2                7                3                41                64                40 
Lost to Follow-up                0                0                0                0                1                0                1                1                0 
Withdrawal by Subject                1                0                0                1                0                1                3                3                0 
: Study ongoing at cutoff date                1                0                0                0                8                2                24                16                1 
: Randomized, not treated                0                0                0                0                0                0                2                4                3 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Phase 1B: Glasdegib + LDAC Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
Phase 1B: Glasdegib + Decitabine Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
Phase 1B: Glasdegib + Cytarabine/Daunorubicin Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Phase 2 Unfit: Glasdegib 100 mg + LDAC Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.
Phase 2 Unfit: LDAC Alone Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.
Total Total of all reporting groups

Baseline Measures
   Phase 1B: Glasdegib + LDAC   Phase 1B: Glasdegib + Decitabine   Phase 1B: Glasdegib + Cytarabine/Daunorubicin   Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin   Phase 2 Unfit: Glasdegib 100 mg + LDAC   Phase 2 Unfit: LDAC Alone   Total 
Overall Participants Analyzed 
[Units: Participants]
 23   7   22   71   88   44   255 
Age 
[Units: Years]
Mean (Standard Deviation)
 75.8  (6.5)   75.0  (4.4)   54.9  (12.7)   61.9  (9.6)   76.2  (6.2)   74.5  (4.9)   66.8  (13.9) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
             
Female      8  34.8%      2  28.6%      10  45.5%      28  39.4%      19  21.6%      18  40.9%      85  33.3% 
Male      15  65.2%      5  71.4%      12  54.5%      43  60.6%      69  78.4%      26  59.1%      170  66.7% 


  Outcome Measures

1.  Primary:   Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B   [ Time Frame: Arms A and B: Cycle 1, Day 1 to Day 28; Arm C: Cycle 1, Day -3 to Day 21 or to Day 28 depending on when the next chemotherapy cycle was started ]

2.  Primary:   Percentage of Participants With Complete Response (CR) at Phase 2 Fit   [ Time Frame: 1 year ]

3.  Primary:   Overall Survival (OS) at Phase 2 Unfit   [ Time Frame: Randomization to Follow-up (4 years) ]

4.  Secondary:   Overall Survival (OS) at Phase 1B   [ Time Frame: First dose to Follow-up (4 years) ]

5.  Secondary:   Overall Survival (OS) at Phase 2 Fit   [ Time Frame: First dose to Follow-up (4 years) ]

6.  Secondary:   Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B   [ Time Frame: 1 year ]

7.  Secondary:   Percentage of Participants With Complete Response (CR) at Phase 2 Unfit   [ Time Frame: 1 year ]

8.  Secondary:   Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit   [ Time Frame: 1 year ]

9.  Secondary:   Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit   [ Time Frame: 1 year ]

10.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21   [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21 ]

11.  Secondary:   Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21   [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21 ]

12.  Secondary:   Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21   [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21 ]

13.  Secondary:   Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1   [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1 ]

14.  Secondary:   Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1   [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1 ]

15.  Secondary:   AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1   [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1 ]

16.  Secondary:   Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10   [ Time Frame: Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10 ]

17.  Secondary:   Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10   [ Time Frame: Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10 ]

18.  Secondary:   AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10   [ Time Frame: Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10 ]

19.  Secondary:   Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10   [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10 ]

20.  Secondary:   Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10   [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10 ]

21.  Secondary:   Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10   [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10 ]

22.  Secondary:   Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10   [ Time Frame: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10 ]

23.  Secondary:   Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2   [ Time Frame: Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2 ]

24.  Secondary:   Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2   [ Time Frame: Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2 ]

25.  Secondary:   AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2   [ Time Frame: Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2 ]

26.  Secondary:   AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3   [ Time Frame: Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3 ]

27.  Secondary:   Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3   [ Time Frame: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3 ]

28.  Secondary:   Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3   [ Time Frame: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3 ]

29.  Secondary:   AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3   [ Time Frame: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3 ]

30.  Secondary:   Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10   [ Time Frame: Pre-dose, 1 and 4 hours post-dose on Induction Cycle 1/Day 10 ]

31.  Secondary:   Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10   [ Time Frame: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10 ]

32.  Secondary:   Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10   [ Time Frame: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10 ]

33.  Secondary:   AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10   [ Time Frame: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10 ]

34.  Secondary:   Number of Participants With Disease-related Gene Mutations at Phase 1B   [ Time Frame: Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm) ]

35.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline   [ Time Frame: Baseline (Induction Cycle 1/Day -3 pre-dose) ]

36.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3   [ Time Frame: Induction Cycle 1/Day 3, 1 Hour Post dose ]

37.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10   [ Time Frame: Induction Cycle 1/Day 10, 1 Hour Post dose ]

38.  Secondary:   Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B   [ Time Frame: Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm) ]

39.  Secondary:   Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In   [ Time Frame: Induction Cycle 1/Lead-in, 1 Hour Post dose ]

40.  Secondary:   Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3   [ Time Frame: Induction Cycle 1/Day 3, 1 Hour Post dose ]

41.  Secondary:   Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit   [ Time Frame: Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit) ]

42.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3   [ Time Frame: Induction Cycle 1/Day 3, 1 Hour Post dose ]

43.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10   [ Time Frame: Induction Cycle 1/Day 10, 1 Hour Post dose ]

44.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1   [ Time Frame: Consolidation Cycle 1/Day 1, 1 Hour Post dose ]

45.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10   [ Time Frame: Consolidation Cycle 1/Day 10, Pre-dose ]

46.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment   [ Time Frame: End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year) ]

47.  Secondary:   Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit   [ Time Frame: Baseline (Induction Cycle 1/Day -3 pre-dose) ]

48.  Secondary:   Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3   [ Time Frame: Induction Cycle 1/Day 3, 1 Hour Post dose ]

49.  Secondary:   Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10   [ Time Frame: Induction Cycle 1/Day 10, 1 Hour Post dose ]

50.  Secondary:   Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment   [ Time Frame: End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year) ]

51.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1   [ Time Frame: Cycle 1/Day 1, 1 Hour Post dose ]

52.  Secondary:   Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10   [ Time Frame: Cycle 1/Day 10, Pre-dose ]

53.  Secondary:   Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit   [ Time Frame: Baseline (Cycle 1/Day 1 pre-dose) ]

54.  Secondary:   Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1   [ Time Frame: Cycle 1/Day 1, 1 Hour Post-dose ]

55.  Secondary:   Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment   [ Time Frame: End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year) ]

56.  Secondary:   Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3   [ Time Frame: Baseline (Induction Cycle 1/Day -3 pre-dose); Induction Cycle 1/Day 3, 1 Hour Post dose ]

57.  Secondary:   Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment   [ Time Frame: Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year) ]

58.  Secondary:   Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment   [ Time Frame: Baseline (Cycle 1/Day 1 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year) ]

59.  Secondary:   Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit   [ Time Frame: Baseline (Induction Cycle 1/Day -3 pre-dose) ]

60.  Secondary:   Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit   [ Time Frame: Baseline (Cycle 1/Day 1 pre-dose) ]

61.  Secondary:   Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit   [ Time Frame: Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year) ]

62.  Secondary:   Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit   [ Time Frame: Baseline (Cycle 1/Day 1 pre-dose); Cycle 1/Day 1, 1 Hour Post dose ]

63.  Secondary:   Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B   [ Time Frame: 1 year ]

64.  Secondary:   Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit   [ Time Frame: 1 year ]

65.  Secondary:   Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)   [ Time Frame: 1 year ]

66.  Secondary:   Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)   [ Time Frame: 1 year ]

67.  Secondary:   Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B   [ Time Frame: 1 year ]

68.  Secondary:   Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)   [ Time Frame: 1 year ]

69.  Secondary:   Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)   [ Time Frame: 1 year ]

70.  Secondary:   Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit   [ Time Frame: 1 year ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com



Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01546038     History of Changes
Other Study ID Numbers: B1371003
2012-000684-24 ( EudraCT Number )
First Submitted: March 1, 2012
First Posted: March 7, 2012
Results First Submitted: December 11, 2017
Results First Posted: May 23, 2018
Last Update Posted: May 23, 2018