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A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients (BRIGHT 1012)

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ClinicalTrials.gov Identifier: NCT02367456
Recruitment Status : Active, not recruiting
First Posted : February 20, 2015
Results First Posted : March 5, 2021
Last Update Posted : April 22, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Myelodysplastic Syndrome
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Interventions Drug: PF-04449913 (Glasdegib)
Drug: Azacitidine
Enrollment 73
Recruitment Details  
Pre-assignment Details

12 participants were enrolled and received the combination treatment of glasdegib and azacitidine in the Lead-in Cohort (LIC).

31 participants were enrolled in the acute myeloid leukemia (AML) cohort. 1 participant withdrew consent before receiving treatment. 30 participants received the combination treatment of glasdegib and azacitidine.

30 participants were enrolled in the myelodysplastic syndrome (MDS) cohort and received the combination treatment of glasdegib and azacitidine.

Arm/Group Title Lead-in Cohort AML Cohort MDS Cohort
Hide Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit drug-drug interaction (DDI) evaluation. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Period Title: Overall Study
Started 12 30 30
Completed 0 0 0
Not Completed 12 30 30
Reason Not Completed
Death             8             21             14
Lost to Follow-up             1             3             1
Ongoing             0             6             15
Other reason             3             0             0
Arm/Group Title Lead-in Cohort AML Cohort MDS Cohort Total
Hide Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Total of all reporting groups
Overall Number of Baseline Participants 12 30 30 72
Hide Baseline Analysis Population Description
Baseline analysis population included all participants enrolled and treated.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 30 participants 30 participants 72 participants
<18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
18-44 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
45-64 years
3
  25.0%
3
  10.0%
7
  23.3%
13
  18.1%
>=65 years
9
  75.0%
27
  90.0%
23
  76.7%
59
  81.9%
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 30 participants 30 participants 72 participants
<75 years
7
  58.3%
16
  53.3%
22
  73.3%
45
  62.5%
>=75 years
5
  41.7%
14
  46.7%
8
  26.7%
27
  37.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 30 participants 30 participants 72 participants
Female
5
  41.7%
12
  40.0%
6
  20.0%
23
  31.9%
Male
7
  58.3%
18
  60.0%
24
  80.0%
49
  68.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 30 participants 30 participants 72 participants
Hispanic or Latino
0
   0.0%
1
   3.3%
2
   6.7%
3
   4.2%
Not Hispanic or Latino
12
 100.0%
23
  76.7%
23
  76.7%
58
  80.6%
Unknown or Not Reported
0
   0.0%
6
  20.0%
5
  16.7%
11
  15.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 30 participants 30 participants 72 participants
White
11
  91.7%
22
  73.3%
24
  80.0%
57
  79.2%
Black or African American
0
   0.0%
1
   3.3%
0
   0.0%
1
   1.4%
Asian
1
   8.3%
1
   3.3%
0
   0.0%
2
   2.8%
Other
0
   0.0%
0
   0.0%
1
   3.3%
1
   1.4%
Unknown
0
   0.0%
6
  20.0%
5
  16.7%
11
  15.3%
Not reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC)
Hide Description An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. Grades of AEs were defined by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 up to 28 days after last dose of study drug or beginning of new anti-cancer therapy (assessed up to 16 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
All-causality TEAEs
12
 100.0%
Treatment-related TEAEs
12
 100.0%
Maximum Grade 3 or 4 TEAEs
8
  66.7%
2.Primary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) in the LIC
Hide Description An serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator. Grades of AEs were defined by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 up to 28 days after last dose of study drug or beginning of new anti-cancer therapy (assessed up to 16 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
All-causality SAEs
9
  75.0%
Treatment-related SAEs
7
  58.3%
3.Primary Outcome
Title Number of Participants With Laboratory Abnormalities in the LIC
Hide Description Laboratory parameters included: hematology parameters (activated partial thromboplastin time, hemoglobin, INR, lymphocyte count, neutrophil count, platelet count, white blood cell), chemistry parameters (alanine aminotransferase, aspartate aminotransferase, alkaline aminotransferase, blood bilirubin, CPK, creatinine, calcium, blood glucose, potassium, magnesium, sodium, albumin, phosphate). Grades of laboratory abnormalities were defined by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 17 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
Activated partial thromboplastin time prolonged Number Analyzed 10 participants
5
  50.0%
Anemia Number Analyzed 12 participants
12
 100.0%
Hemoglobin increased Number Analyzed 12 participants
0
   0.0%
INR increased Number Analyzed 11 participants
8
  72.7%
Lymphocyte count decreased Number Analyzed 12 participants
9
  75.0%
Lymphocyte count increased Number Analyzed 12 participants
3
  25.0%
Neutrophil count decreased Number Analyzed 12 participants
10
  83.3%
Platelet count decreased Number Analyzed 12 participants
12
 100.0%
White blood cell decreased Number Analyzed 12 participants
11
  91.7%
Alanine aminotransferase increased Number Analyzed 12 participants
4
  33.3%
Alkaline phosphatase increase Number Analyzed 12 participants
0
   0.0%
Aspartate aminotransferase increased Number Analyzed 12 participants
2
  16.7%
Blood bilirubin increased Number Analyzed 12 participants
6
  50.0%
CPK increased Number Analyzed 11 participants
0
   0.0%
Creatinine increased Number Analyzed 12 participants
11
  91.7%
Hypercalcemia Number Analyzed 12 participants
1
   8.3%
Hyperglycemia Number Analyzed 12 participants
1
   8.3%
Hyperkalemia Number Analyzed 12 participants
3
  25.0%
Hypermagnesemia Number Analyzed 12 participants
2
  16.7%
Hypernatremia Number Analyzed 12 participants
1
   8.3%
Hypoalbuminemia Number Analyzed 12 participants
5
  41.7%
Hypocalcemia Number Analyzed 12 participants
3
  25.0%
Hypoglycemia Number Analyzed 12 participants
1
   8.3%
Hypokalemia Number Analyzed 12 participants
3
  25.0%
Hypomagnesemia Number Analyzed 12 participants
2
  16.7%
Hyponatremia Number Analyzed 12 participants
6
  50.0%
Hypophosphatemia Number Analyzed 12 participants
4
  33.3%
4.Primary Outcome
Title Percentage of Participants Achieving Complete Remission (CR) in the AML and MDS Cohorts
Hide Description

Percentage of participants achieving CR as defined by the 2017 European Leukemia Net (ELN) Response Criteria for all participants with AML and modified International Working Group (IWG) criteria (2006) for all participants with MDS in the expansion cohorts.

For AML cohort, CR was defined as neutrophils ≥ 1 x 10^9/L, platelets ≥ 1 x 10^11/L, percentage of bone marrow blasts (BMB) <5% with no peripheral blasts and no blasts with Auer rods, no extramedullary disease (EMD), and transfusion independent.

For MDS cohort, CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10^9/L, platelets ≥1 x 10^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks.

Time Frame Cycle 1 Day 1 to End of Treatment (EoT) visit (within 14 days after last dose) (assessed up to 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
20.0
(7.7 to 38.6)
13.3
(3.8 to 30.7)
5.Secondary Outcome
Title Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC
Hide Description RR (Percentage of participants achieving CR+PR among all the enrolled and treated patients as defined by modified International Working Group (IWG) criteria (2006)) in the LIC. CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10^9/L, platelets ≥1 x 10^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks. PR was defined as meeting all CR criteria if abnormal before treatment except BMB, percentage of BMB decreased by ≥50% but still >5% for at least 4 weeks.
Time Frame Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study treatment.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: Percentage of participants
25.0
6.Secondary Outcome
Title Number of Participants With Efficacy Measures Other Than CR in the LIC
Hide Description Number of participants with efficacy measures other than CR as defined by modified IWG criteria (2006) in LIC, including marrow CR(mCR), stable disease(SD), hematologic improvement(HI). CR: hemoglobin≥11 g/dL, neutrophils≥1 x 10^9/L, platelets≥1 x 10^11/L, percentage of blasts=0%, percentage of BMB≤5%, normal maturation of all cell lines (note if has persistent dysplasia), all responses last at least 4 weeks. mCR: BMB≤5% & decreased by≥50%. SD: failure to achieve PR, no evidence of progression. HI: erythroid response (pretreatment<11g/dL): hemoglobin increase by≥1.5 g/dL, relevant reduction of units of red blood cell transfusions by at least 4 transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks; platelet response (pretreatment<1x10^11/L): increase of≥30x10^9/L if starting with >20x10^9/L, and increase from <20x10^9/L to >20x10^9/L and by at least 100%; neutrophil response (pretreatment<1x10^9/L): at least a 100% increase, absolute increase >0.5x10^9/L
Time Frame Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set was defined as all participants who received at least 1 dose of any study treatment.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
Marrow CR (mCR)
2
  16.7%
Stable disease (SD)
4
  33.3%
Hematologic improvement (HI) of at least 1 lineage
6
  50.0%
7.Secondary Outcome
Title Number of Participants With TEAEs in the AML and MDS Cohorts
Hide Description An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. AEs were graded by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
All-causality TEAEs
30
 100.0%
30
 100.0%
Treatment-related TEAEs
29
  96.7%
29
  96.7%
8.Secondary Outcome
Title Number of Participants With SAEs in the AML and MDS Cohorts
Hide Description A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator. AEs were graded by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of study treatment
Arm/Group Title AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
All-causality SAEs
24
  80.0%
18
  60.0%
Treatment-related SAEs
8
  26.7%
8
  26.7%
9.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts
Hide Description Laboratory parameters included: hematology parameters (activated partial thromboplastin time, hemoglobin, INR, lymphocyte count, neutrophil count, platelet count, white blood cell), chemistry parameters (alanine aminotransferase, aspartate aminotransferase, alkaline aminotransferase, blood bilirubin, CPK, creatinine, calcium, blood glucose, potassium, magnesium, sodium, albumin, phosphate). Laboratory abnormalities were graded by NCI CTCAE version 4.03.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
Activated partial thromboplastin time prolonged Number Analyzed 2 participants 2 participants
0
   0.0%
0
   0.0%
Anemia Number Analyzed 30 participants 29 participants
30
 100.0%
29
 100.0%
Hemoglobin increased Number Analyzed 30 participants 29 participants
0
   0.0%
0
   0.0%
INR increased Number Analyzed 2 participants 2 participants
0
   0.0%
1
  50.0%
Lymphocyte count decreased Number Analyzed 30 participants 27 participants
23
  76.7%
23
  85.2%
Lymphocyte count increased Number Analyzed 30 participants 27 participants
6
  20.0%
1
   3.7%
Neutrophil count decreased Number Analyzed 30 participants 28 participants
25
  83.3%
25
  89.3%
Platelet count decreased Number Analyzed 30 participants 29 participants
29
  96.7%
26
  89.7%
White blood cell decreased Number Analyzed 30 participants 29 participants
22
  73.3%
27
  93.1%
Alanine aminotransferase increased Number Analyzed 30 participants 29 participants
13
  43.3%
12
  41.4%
Alkaline phosphatase increased Number Analyzed 30 participants 29 participants
7
  23.3%
7
  24.1%
Aspartate aminotransferase increased Number Analyzed 30 participants 29 participants
11
  36.7%
8
  27.6%
Blood bilirubin increased Number Analyzed 30 participants 29 participants
3
  10.0%
10
  34.5%
CPK increased Number Analyzed 29 participants 28 participants
5
  17.2%
4
  14.3%
Creatinine increased Number Analyzed 30 participants 29 participants
29
  96.7%
28
  96.6%
Hypercalcemia Number Analyzed 30 participants 29 participants
3
  10.0%
0
   0.0%
Hyperglycemia Number Analyzed 30 participants 29 participants
3
  10.0%
4
  13.8%
Hyperkalemia Number Analyzed 30 participants 29 participants
6
  20.0%
6
  20.7%
Hypermagnesemia Number Analyzed 30 participants 29 participants
1
   3.3%
2
   6.9%
Hypernatremia Number Analyzed 30 participants 29 participants
2
   6.7%
1
   3.4%
Hypoalbuminemia Number Analyzed 30 participants 29 participants
22
  73.3%
17
  58.6%
Hypocalcemia Number Analyzed 30 participants 29 participants
3
  10.0%
11
  37.9%
Hypoglycemia Number Analyzed 30 participants 29 participants
4
  13.3%
2
   6.9%
Hypokalemia Number Analyzed 30 participants 29 participants
8
  26.7%
3
  10.3%
Hypomagnesemia Number Analyzed 30 participants 29 participants
12
  40.0%
9
  31.0%
Hyponatremia Number Analyzed 30 participants 29 participants
18
  60.0%
12
  41.4%
Hypophosphatemia Number Analyzed 30 participants 29 participants
13
  43.3%
7
  24.1%
10.Secondary Outcome
Title Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort
Hide Description Number of participants with CR with partial hematologic recovery (CRh), CR with incomplete blood count recovery (CRi), partial remission (PR), stable disease (SD), and morphologic leukemia free state (MLFS). CRh: neutrophils>5x10^8/L, platelets>5x10^10/L, BMB<5%, no peripheral blasts, no blasts with Auer rods, no extramedullary disease (EMD), not qualifying for CR. CRi: neutrophils <1x10^9/L or platelets<1x10^11/L; BMB <5%, no peripheral blasts, no blasts with Auer rods; no EMD; neutrophils or platelets not recovered; not qualifying for CRh. PR: neutrophils ≥1x10^9/L; platelets ≥1x10^11/L; blasts decreased to 5-25% and ≥50% decrease from pretreatment; blasts≤5% if Auer rod positive. SD: ≥3 months of absence of CR without minimal residual disease (CRMRD-), CR, CRh, CRi, PR, and MLFS, criteria for PD not met. MLFS: neutrophils <1x10^9/L and platelets<1x10^11/L, BMB<5%, no blasts with Auer rods; no EMD; neutrophils and platelets not recovered; not qualifying for CRi
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
CRh
0
   0.0%
CRi
1
   3.3%
PR
2
   6.7%
MLFS
1
   3.3%
SD
6
  20.0%
11.Secondary Outcome
Title Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort
Hide Description Number of participants with PR, marrow CR (mCR), SD, complete or partial cytogenetic response, and hematologic improvement (HI). PR: BMB >5% and decreased by ≥50% (at least 4 weeks), meeting all CR criteria if abnormal before treatment except BMB. mCR: BMB ≤5% and decreased by ≥50%. SD: failure to achieve PR, no evidence of progression. Complete or partial cytogenic response: disappearance of chromosomal abnormality without new ones, or ≥ 50% reduction of chromosomal abnormality. HI: erythroid response (pretreatment <11g/dL): hemoglobin increase by≥1.5 g/dL, relevant reduction of units of red blood cell transfusions by at least 4 transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks; platelet response (pretreatment <1x10^11/L): increase of ≥30x10^9/L if starting with >20x10^9/L, and increase from <20x10^9/L to >20x10^9/L and by at least 100%; neutrophil response (pretreatment <1x10^9/L): at least a 100% increase, absolute increase >0.5x10^9/L.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 22 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
PR
3
  10.0%
mCR
5
  16.7%
SD
8
  26.7%
Complete cytogenetic response
3
  10.0%
Partial cytogenetic response
1
   3.3%
HI of at least 1 lineage
9
  30.0%
HI of at least 1 lineage without CR or PR
3
  10.0%
12.Secondary Outcome
Title Kaplan-Meier Estimate of Median Overall Survival (OS) in the AML and MDS Cohorts
Hide Description Overall survival (OS) was defined as the time from date of first study treatment to date of death from any cause. Patients last known to be alive were to be censored at the date of last contact. OS was analyzed and displayed graphically for each expansion cohort separately using the Kaplan-Meier method. The median event time and corresponding two-sided 95%CI were provided for each cohort. OS was first analyzed when the primary endpoint of CR was analyzed in the respective expansion cohort.
Time Frame Cycle 1 Day 1 to date of death from any cause (assessed up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30 30
Median (95% Confidence Interval)
Unit of Measure: Months
9.2
(6.2 to 14.0)
15.8
(9.3 to 21.9)
13.Secondary Outcome
Title Duration of CR in the AML and MDS Cohorts
Hide Description Duration of CR was defined as the duration from date of first achieving CR to the date of disease progression (relapse) after CR, or death due to any cause. Participants last known to be alive who were free from disease progression or relapse after CR were censored at the date of the last assessment that verified their disease status. Duration of CR was analyzed using the Kaplan-Meier method. Disease progression was defined as: percentage of bone marrow blasts increased by ≥50% to >5% (for participants with <5% blasts at screening), >10% (for participants with 5-10% blasts at screening), >20% (for participants with 11-20% blasts at screening) or >30% (for participants with 21-30% blasts at screening), and with any of the following condition: at least 50% decrease from maximum remission/response in granulocytes or platelets; reduction in hemoglobin by ≥2 g/dL; transfusion dependence.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30 30
Median (Full Range)
Unit of Measure: Months
4.73
(0.03 to 7.85)
3.71
(0.72 to 8.18)
14.Secondary Outcome
Title Time to CR in the AML and MDS Cohorts
Hide Description Time to CR was defined for participants in the expansion cohorts who had achieved response on study as the time from date of the first dose of study drug to date of the first documentation of response. Time to CR was analyzed using the Kaplan-Meier method.
Time Frame Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis population included all participants who received at least 1 dose of any study treatment.
Arm/Group Title AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30 30
Median (Full Range)
Unit of Measure: Months
5.54
(3.12 to 5.98)
4.39
(3.71 to 5.55)
15.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort
Hide Description Maximum plasma concentration of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The PK concentration analysis set included all participants who received treatment and had at least 1 value of analyte concentration of glasdegib or azacitidine available.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
C1D7 Number Analyzed 12 participants
1013
(58%)
C1D15 Number Analyzed 9 participants
991.4
(57%)
16.Secondary Outcome
Title Area Under the Plasma Concentration Curve From Time Zero to End of Dosing Interval (AUCtau) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort
Hide Description Area under the plasma concentration curve from time zero to end of dosing interval (AUCtau) of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
C1D7 Number Analyzed 12 participants
13230
(49%)
C1D15 Number Analyzed 9 participants
14350
(61%)
17.Secondary Outcome
Title Time to First Occurrence of Maximum Plasma Concentration (Tmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort
Hide Description Time to first occurrence of maximum plasma concentration of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: hr
C1D7 Number Analyzed 12 participants
1.050
(1.00 to 5.70)
C1D15 Number Analyzed 9 participants
1.500
(1.00 to 6.02)
18.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort
Hide Description Maximum plasma concentration of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK concentration analysis set included all participants who received treatment and had at least 1 value of analyte concentration of glasdegib or azacitidine available.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
C1D1
778.5
(23%)
C1D7
716.9
(32%)
19.Secondary Outcome
Title Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort
Hide Description Area under the plasma concentration curve from time zero to extrapolated infinite time (AUCinf) of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
C1D1
1319
(19%)
C1D7
1260
(21%)
20.Secondary Outcome
Title Tmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort
Hide Description Time to first occurrence of maximum plasma concentration of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.
Time Frame 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1; pre-dose and 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 7.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.
Arm/Group Title Lead-in Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Overall Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: hr
C1D1
0.5000
(0.000 to 1.00)
C1D7
0.5000
(0.250 to 1.08)
21.Secondary Outcome
Title Trough Plasma Concentration (Ctrough) of Glasdegib on C1D15 and C2D1 in the AML and MDS Cohorts
Hide Description Trough plasma concentration was defined as the estimated lowest concentration before next dose administration.
Time Frame Pre-dose and 1 and 4 hours post-dose on Cycle 1 Day 15 and Cycle 2 Day 1.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK concentration analysis set included all participants who received treatment and had at least 1 value of analyte concentration of glasdegib or azacitidine available.
Arm/Group Title AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 30 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
C1D15 Number Analyzed 25 participants 17 participants
468.440
(88%)
308.144
(95%)
C2D1 Number Analyzed 17 participants 18 participants
462.806
(110%)
167.483
(52%)
22.Secondary Outcome
Title Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts
Hide Description Number of participants that met categorical criteria of QTcF values in LIC, AML and MDS cohorts
Time Frame Cycle 1 Day 1 to EoT visit (assessed up to 16 months in the LIC cohort and 24 months in the AML and MDS cohorts)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lead-in Cohort AML Cohort MDS Cohort
Hide Arm/Group Description:
Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Number of Participants Analyzed 12 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
Maximum QTcF interval <450 ms
5
  41.7%
16
  53.3%
18
  60.0%
450 ms <=Maximum QTcF interval <480 ms
2
  16.7%
6
  20.0%
6
  20.0%
480 ms <=Maximum QTcF interval <500 ms
4
  33.3%
5
  16.7%
4
  13.3%
Maximum QTcF interval ≥500 ms
1
   8.3%
3
  10.0%
2
   6.7%
QTcF maximum increase from baseline <30 ms
3
  25.0%
18
  60.0%
23
  76.7%
30 ms <= QTcF maximum increase <60 ms
7
  58.3%
10
  33.3%
5
  16.7%
QTcF maximum increase from baseline >=60 ms
2
  16.7%
2
   6.7%
2
   6.7%
Time Frame From Cycle 1 Day 1 till up to 28 days after last dose of study drug or beginning of new anti-cancer therapy (assessed up to 16 months in the LIC cohort and 24 months in the AML and MDS cohorts)
Adverse Event Reporting Description The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
 
Arm/Group Title Lead-in Cohort AML Cohort MDS Cohort
Hide Arm/Group Description Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
All-Cause Mortality
Lead-in Cohort AML Cohort MDS Cohort
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/12 (75.00%)   22/30 (73.33%)   15/30 (50.00%) 
Hide Serious Adverse Events
Lead-in Cohort AML Cohort MDS Cohort
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/12 (75.00%)   24/30 (80.00%)   18/30 (60.00%) 
Blood and lymphatic system disorders       
Anaemia * 1  0/12 (0.00%)  1/30 (3.33%)  1/30 (3.33%) 
Febrile neutropenia * 1  4/12 (33.33%)  6/30 (20.00%)  5/30 (16.67%) 
Thrombocytopenia * 1  0/12 (0.00%)  1/30 (3.33%)  1/30 (3.33%) 
Cardiac disorders       
Acute myocardial infarction * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Angina pectoris * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Atrial fibrillation * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Cardiac failure * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Right ventricular failure * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Ascites * 1  0/12 (0.00%)  1/30 (3.33%)  1/30 (3.33%) 
Constipation * 1  1/12 (8.33%)  1/30 (3.33%)  0/30 (0.00%) 
Gastrointestinal haemorrhage * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Nausea * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Upper gastrointestinal haemorrhage * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Vomiting * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
General disorders       
Disease progression * 1  0/12 (0.00%)  3/30 (10.00%)  1/30 (3.33%) 
General physical health deterioration * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Multiple organ dysfunction syndrome * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Pyrexia * 1  2/12 (16.67%)  4/30 (13.33%)  2/30 (6.67%) 
Infections and infestations       
Bacteraemia * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Bronchopulmonary aspergillosis * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Catheter site cellulitis * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Cellulitis * 1  2/12 (16.67%)  0/30 (0.00%)  1/30 (3.33%) 
Cystitis * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Lower respiratory tract infection * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Neutropenic sepsis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Osteomyelitis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Pneumonia * 1  0/12 (0.00%)  1/30 (3.33%)  1/30 (3.33%) 
Pseudomonal sepsis * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Pyelonephritis * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Respiratory tract infection * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Sepsis * 1  0/12 (0.00%)  1/30 (3.33%)  5/30 (16.67%) 
Septic shock * 1  1/12 (8.33%)  1/30 (3.33%)  0/30 (0.00%) 
Streptococcal infection * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Urinary tract infection * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Urosepsis * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Injury, poisoning and procedural complications       
Fall * 1  0/12 (0.00%)  1/30 (3.33%)  1/30 (3.33%) 
Femur fracture * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Lumbar vertebral fracture * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Post procedural haemorrhage * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Sternal fracture * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Subdural haematoma * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Investigations       
Electrocardiogram QT prolonged * 1  1/12 (8.33%)  2/30 (6.67%)  0/30 (0.00%) 
Metabolism and nutrition disorders       
Gout * 1  1/12 (8.33%)  0/30 (0.00%)  1/30 (3.33%) 
Hyponatraemia * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Tumor lysis syndrome * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Musculoskeletal chest pain * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Gastrointestinal lymphoma * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Lung neoplasm malignant * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Metastases to liver * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Myelodysplastic syndrome * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Nervous system disorders       
Cerebral haemorrhage * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Cerebrovascular accident * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Subarachnoid haemorrhage * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Syncope * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Psychiatric disorders       
Depression * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Renal and urinary disorders       
Acute kidney injury * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Renal failure * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory distress syndome * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Epistaxis * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Hypoxia * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Pneumonitis * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Pulmonary arterial hypertension * 1  0/12 (0.00%)  0/30 (0.00%)  1/30 (3.33%) 
Respiratory failure * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
Vascular disorders       
Haematoma * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Hypotension * 1  0/12 (0.00%)  1/30 (3.33%)  1/30 (3.33%) 
Orthostatic hypotension * 1  0/12 (0.00%)  1/30 (3.33%)  0/30 (0.00%) 
1
Term from vocabulary, MedDRA v22.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lead-in Cohort AML Cohort MDS Cohort
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   29/30 (96.67%)   29/30 (96.67%) 
Blood and lymphatic system disorders       
Anaemia * 1  9/12 (75.00%)  6/30 (20.00%)  11/30 (36.67%) 
Febrile neutropenia * 1  0/12 (0.00%)  3/30 (10.00%)  2/30 (6.67%) 
Leukopenia * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Neutropenia * 1  6/12 (50.00%)  0/30 (0.00%)  3/30 (10.00%) 
Thrombocytopenia * 1  3/12 (25.00%)  0/30 (0.00%)  3/30 (10.00%) 
Cardiac disorders       
Atrial fibrillation * 1  0/12 (0.00%)  2/30 (6.67%)  3/30 (10.00%) 
Tachycardia * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Ear and labyrinth disorders       
Ear pain * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Tinnitus * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Eye disorders       
Vision blurred * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  2/12 (16.67%)  6/30 (20.00%)  4/30 (13.33%) 
Abdominal pain upper * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Ascites * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Constipation * 1  9/12 (75.00%)  18/30 (60.00%)  15/30 (50.00%) 
Dental caries * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Diarrhoea * 1  6/12 (50.00%)  16/30 (53.33%)  14/30 (46.67%) 
Dry mouth * 1  2/12 (16.67%)  4/30 (13.33%)  4/30 (13.33%) 
Dysepsia * 1  2/12 (16.67%)  0/30 (0.00%)  2/30 (6.67%) 
Dysphagia * 1  0/12 (0.00%)  0/30 (0.00%)  3/30 (10.00%) 
Enterocolitis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Gastrooesophageal reflux disease * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Gingival bleeding * 1  1/12 (8.33%)  0/30 (0.00%)  2/30 (6.67%) 
Haematochezia * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Haemorrhoids * 1  1/12 (8.33%)  4/30 (13.33%)  2/30 (6.67%) 
Nausea * 1  8/12 (66.67%)  19/30 (63.33%)  20/30 (66.67%) 
Oesophagitis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Oral dysaethesia * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Proctalgia * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Rectal haemorrhage * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Stomatitis * 1  1/12 (8.33%)  2/30 (6.67%)  4/30 (13.33%) 
Vomiting * 1  4/12 (33.33%)  13/30 (43.33%)  10/30 (33.33%) 
General disorders       
Asthenia * 1  2/12 (16.67%)  3/30 (10.00%)  0/30 (0.00%) 
Chest pain * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Chills * 1  1/12 (8.33%)  2/30 (6.67%)  0/30 (0.00%) 
Fatigue * 1  6/12 (50.00%)  8/30 (26.67%)  9/30 (30.00%) 
General physical health deterioration * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Injection site erythema * 1  3/12 (25.00%)  2/30 (6.67%)  0/30 (0.00%) 
Injection site irritation * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Injection site nodule * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Injection site pain * 1  0/12 (0.00%)  3/30 (10.00%)  0/30 (0.00%) 
Injection site reaction * 1  2/12 (16.67%)  2/30 (6.67%)  5/30 (16.67%) 
Oedema peripheral * 1  3/12 (25.00%)  4/30 (13.33%)  8/30 (26.67%) 
Pain * 1  1/12 (8.33%)  5/30 (16.67%)  2/30 (6.67%) 
Pyrexia * 1  2/12 (16.67%)  8/30 (26.67%)  3/30 (10.00%) 
Hepatobiliary disorders       
Ischaemic hepatitis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Jaundice * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Infections and infestations       
Bacteraemia * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Cellulitis * 1  2/12 (16.67%)  0/30 (0.00%)  0/30 (0.00%) 
Device related infection * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Diverticulitis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Folliculitis * 1  3/12 (25.00%)  0/30 (0.00%)  0/30 (0.00%) 
Oral candidiasis * 1  0/12 (0.00%)  4/30 (13.33%)  0/30 (0.00%) 
Pneumonia * 1  3/12 (25.00%)  0/30 (0.00%)  2/30 (6.67%) 
Sepsis * 1  2/12 (16.67%)  0/30 (0.00%)  0/30 (0.00%) 
Sinusitis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Upper respiratory tract infection * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Urinary tract infection * 1  3/12 (25.00%)  2/30 (6.67%)  2/30 (6.67%) 
Injury, poisoning and procedural complications       
Contusion * 1  2/12 (16.67%)  0/30 (0.00%)  5/30 (16.67%) 
Fall * 1  0/12 (0.00%)  8/30 (26.67%)  7/30 (23.33%) 
Postoperative hypotension * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Investigations       
Alanine transferase increased * 1  0/12 (0.00%)  3/30 (10.00%)  4/30 (13.33%) 
Aspartate aminotransferase increase * 1  0/12 (0.00%)  4/30 (13.33%)  5/30 (16.67%) 
Blood alkaline phosphatase increased * 1  0/12 (0.00%)  3/30 (10.00%)  2/30 (6.67%) 
Blood bilirubin increased * 1  2/12 (16.67%)  3/30 (10.00%)  4/30 (13.33%) 
Blood creatine phosphokinase increased * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Blood creatinine increased * 1  0/12 (0.00%)  4/30 (13.33%)  4/30 (13.33%) 
Blood lactate dehydrogenase increased * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
C-reactive protein increased * 1  0/12 (0.00%)  3/30 (10.00%)  0/30 (0.00%) 
Electrocardiogram QT prolonged * 1  5/12 (41.67%)  5/30 (16.67%)  3/30 (10.00%) 
Heart rate irregular * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
International normalised ratio increased * 1  0/12 (0.00%)  3/30 (10.00%)  2/30 (6.67%) 
Lymphocyte count decreased * 1  0/12 (0.00%)  4/30 (13.33%)  4/30 (13.33%) 
Neutrophil count decreased * 1  0/12 (0.00%)  2/30 (6.67%)  11/30 (36.67%) 
Platelet count decreased * 1  0/12 (0.00%)  5/30 (16.67%)  11/30 (36.67%) 
Weight decreased * 1  5/12 (41.67%)  4/30 (13.33%)  5/30 (16.67%) 
White blood cell count decreased * 1  1/12 (8.33%)  7/30 (23.33%)  8/30 (26.67%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  2/12 (16.67%)  16/30 (53.33%)  9/30 (30.00%) 
Hyperglycaemia * 1  0/12 (0.00%)  4/30 (13.33%)  6/30 (20.00%) 
Hyperkalaemia * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Hypernatraemia * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Hyperuricaemia * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Hypoalbuminaemia * 1  0/12 (0.00%)  5/30 (16.67%)  4/30 (13.33%) 
Hypocalcaemia * 1  1/12 (8.33%)  2/30 (6.67%)  0/30 (0.00%) 
Hypokalaemia * 1  1/12 (8.33%)  8/30 (26.67%)  2/30 (6.67%) 
Hypomagnesaemia * 1  2/12 (16.67%)  6/30 (20.00%)  6/30 (20.00%) 
Hyponatraemia * 1  3/12 (25.00%)  7/30 (23.33%)  6/30 (20.00%) 
Hypophosphataemia * 1  2/12 (16.67%)  2/30 (6.67%)  2/30 (6.67%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  0/12 (0.00%)  2/30 (6.67%)  3/30 (10.00%) 
Arthritis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Back pain * 1  0/12 (0.00%)  6/30 (20.00%)  0/30 (0.00%) 
Flank pain * 1  0/12 (0.00%)  3/30 (10.00%)  2/30 (6.67%) 
Haemarthrosis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Muscle spasms * 1  4/12 (33.33%)  9/30 (30.00%)  15/30 (50.00%) 
Muscular weakness * 1  0/12 (0.00%)  4/30 (13.33%)  4/30 (13.33%) 
Myalgia * 1  1/12 (8.33%)  2/30 (6.67%)  5/30 (16.67%) 
Neck pain * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Pain in extremity * 1  2/12 (16.67%)  0/30 (0.00%)  0/30 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Melanocytic naevus * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Nervous system disorders       
Ageusia * 1  0/12 (0.00%)  2/30 (6.67%)  2/30 (6.67%) 
Amnesia * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Dizziness * 1  2/12 (16.67%)  3/30 (10.00%)  7/30 (23.33%) 
Dizziness postural * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Dysgeusia * 1  5/12 (41.67%)  4/30 (13.33%)  13/30 (43.33%) 
Headache * 1  0/12 (0.00%)  3/30 (10.00%)  7/30 (23.33%) 
Hypoaesthesia * 1  1/12 (8.33%)  0/30 (0.00%)  3/30 (10.00%) 
Hypogeusia * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Paraesthesia * 1  0/12 (0.00%)  4/30 (13.33%)  0/30 (0.00%) 
Presyncope * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Taste disorder * 1  1/12 (8.33%)  3/30 (10.00%)  0/30 (0.00%) 
Psychiatric disorders       
Anxiety * 1  1/12 (8.33%)  4/30 (13.33%)  0/30 (0.00%) 
Delirium * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Depression * 1  1/12 (8.33%)  0/30 (0.00%)  2/30 (6.67%) 
Insomnia * 1  2/12 (16.67%)  6/30 (20.00%)  5/30 (16.67%) 
Mental status change * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Sleep disorder * 1  0/12 (0.00%)  3/30 (10.00%)  3/30 (10.00%) 
Renal and urinary disorders       
Acute kidney injury * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Dysuria * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Haematuria * 1  2/12 (16.67%)  2/30 (6.67%)  0/30 (0.00%) 
Pollakiuria * 1  3/12 (25.00%)  0/30 (0.00%)  2/30 (6.67%) 
Renal failure * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Urinary incontinence * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Urinary retention * 1  2/12 (16.67%)  0/30 (0.00%)  0/30 (0.00%) 
Urinary tract pain * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Atelectasis * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Cough * 1  3/12 (25.00%)  7/30 (23.33%)  5/30 (16.67%) 
Dysphonia * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Dyspnoea * 1  4/12 (33.33%)  8/30 (26.67%)  6/30 (20.00%) 
Dyspnoea exertional * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Epistaxis * 1  1/12 (8.33%)  4/30 (13.33%)  4/30 (13.33%) 
Hiccups * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Hypoxia * 1  2/12 (16.67%)  0/30 (0.00%)  0/30 (0.00%) 
Nasal congestion * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Oropharyngeal pain * 1  2/12 (16.67%)  4/30 (13.33%)  0/30 (0.00%) 
Pleural effusion * 1  1/12 (8.33%)  3/30 (10.00%)  0/30 (0.00%) 
Respiratory distress * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Rhinorrhoea * 1  4/12 (33.33%)  2/30 (6.67%)  2/30 (6.67%) 
Tachypnoea * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Skin and subcutaneous tissue disorders       
Acne * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Alopecia * 1  4/12 (33.33%)  2/30 (6.67%)  7/30 (23.33%) 
Dermatitis acneiform * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Ecchymosis * 1  2/12 (16.67%)  0/30 (0.00%)  0/30 (0.00%) 
Erythema * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Night sweats * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Pruitus * 1  1/12 (8.33%)  0/30 (0.00%)  2/30 (6.67%) 
Purpura * 1  0/12 (0.00%)  0/30 (0.00%)  3/30 (10.00%) 
Rash * 1  3/12 (25.00%)  3/30 (10.00%)  3/30 (10.00%) 
Rash maculo-papular * 1  0/12 (0.00%)  0/30 (0.00%)  2/30 (6.67%) 
Skin disorder * 1  0/12 (0.00%)  2/30 (6.67%)  0/30 (0.00%) 
Skin ulcer * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Vascular disorders       
Deep vein thrombosis * 1  0/12 (0.00%)  3/30 (10.00%)  0/30 (0.00%) 
Haematoma * 1  2/12 (16.67%)  3/30 (10.00%)  0/30 (0.00%) 
Haemorrhage * 1  1/12 (8.33%)  0/30 (0.00%)  0/30 (0.00%) 
Hypertension * 1  0/12 (0.00%)  3/30 (10.00%)  0/30 (0.00%) 
Hypotension * 1  2/12 (16.67%)  3/30 (10.00%)  8/30 (26.67%) 
1
Term from vocabulary, MedDRA v22.1
*
Indicates events were collected by non-systematic assessment
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 8007181021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02367456    
Other Study ID Numbers: B1371012
2014-001345-24 ( EudraCT Number )
BRIGHT MDS&AML1012 ( Other Identifier: Alias Study Number )
First Submitted: February 13, 2015
First Posted: February 20, 2015
Results First Submitted: January 19, 2021
Results First Posted: March 5, 2021
Last Update Posted: April 22, 2021