BRIGHT 1012: A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients
Study Details
Study Description
Brief Summary
This multi center open label Phase 1b study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of glasdegib (PF-04449913) when combined with azacitidine in patients with previously untreated Higher Risk Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML). This clinical study includes two components: (a) a safety lead in cohort (LIC) and (b) an expansion phase with an AML cohort and an MDS cohort.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm A MDS patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2 |
Drug: PF-04449913 (Glasdegib)
Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles
Drug: Azacitidine
75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle
|
Experimental: Arm B AML patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2 |
Drug: PF-04449913 (Glasdegib)
Daily dose of PF-04449913 100mg tablet in a continuous regimen of 28 day cycles
Drug: Azacitidine
75mg/m2 on Days 1-7 (+/- 3 days for each dose) of a 28 day cycle
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) [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)]
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.
- Number of Participants With Serious Adverse Events (SAEs) in the LIC [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)]
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.
- Number of Participants With Laboratory Abnormalities in the LIC [Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 17 months)]
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.
- Percentage of Participants Achieving Complete Remission (CR) in the AML and MDS Cohorts [Cycle 1 Day 1 to End of Treatment (EoT) visit (within 14 days after last dose) (assessed up to 22 months)]
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.
Secondary Outcome Measures
- Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC [Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 18 months)]
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.
- Number of Participants With Efficacy Measures Other Than CR in the LIC [Cycle 1 Day 1 to last follow up visit (at least 28 days after discontinuation of treatment) (assessed up to 18 months)]
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
- Number of Participants With TEAEs in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]
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.
- Number of Participants With SAEs in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]
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.
- Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]
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.
- Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 20 months)]
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
- Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 22 months)]
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.
- Kaplan-Meier Estimate of Median Overall Survival (OS) in the AML and MDS Cohorts [Cycle 1 Day 1 to date of death from any cause (assessed up to 24 months)]
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.
- Duration of CR in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]
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 to CR in the AML and MDS Cohorts [Cycle 1 Day 1 to EoT visit (within 14 days after last dose) (assessed up to 24 months)]
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.
- Maximum Plasma Concentration (Cmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort [Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15]
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.
- 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 [Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15]
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 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 [Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Day 15]
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.
- Maximum Plasma Concentration (Cmax) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort [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.]
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.
- 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 [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.]
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.
- Tmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort [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.]
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.
- Trough Plasma Concentration (Ctrough) of Glasdegib on C1D15 and C2D1 in the AML and MDS Cohorts [Pre-dose and 1 and 4 hours post-dose on Cycle 1 Day 15 and Cycle 2 Day 1.]
Trough plasma concentration was defined as the estimated lowest concentration before next dose administration.
- Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts [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)]
Number of participants that met categorical criteria of QTcF values in LIC, AML and MDS cohorts
Eligibility Criteria
Criteria
Inclusion criteria:
-
Patients must have previously untreated MDS, AML, or CMML according to the WHO 2016 classification.
-
MDS patients must have Intermediate (>3 to 4.5 points), High Risk (>4.5 - 6) or Very High Risk (>6 points) disease according to the Revised International Prognostic Scoring System 2012 (IPSS-R).
-
Clinical indication for treatment with azacitidine for MDS or AML.
Exclusion criteria:
-
Patients with AML who are candidates for standard induction chemotherapy as first line treatment.
-
Patients with known active CNS leukemia.
-
Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Alabama at Birmingham the Kirklin Clinic | Birmingham | Alabama | United States | 35233 |
2 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35249 |
3 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
4 | Smilow Cancer Center at Yale New Haven Hospital | New Haven | Connecticut | United States | 06510 |
5 | The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | United States | 21287 |
6 | Montefiore Einstein Center for Cancer | Bronx | New York | United States | 10461 |
7 | Montefiore Medical Center | Bronx | New York | United States | 10467 |
8 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
9 | Stony Brook University Hospital Cancer Center | Stony Brook | New York | United States | 11794 |
10 | Stony Brook University | Stony Brook | New York | United States | 11794 |
11 | Duke University Health System: Adult Bone Marrow Transplant Clinic | Durham | North Carolina | United States | 27705 |
12 | Duke University Health System, Duke University Hospital | Durham | North Carolina | United States | 27710 |
13 | Duke University Health System | Durham | North Carolina | United States | 27710 |
14 | Investigational Chemotherapy Service | Durham | North Carolina | United States | 27710 |
15 | Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio | United States | 44195 |
16 | Henry-Joyce Cancer Center | Nashville | Tennessee | United States | 37232 |
17 | Vanderbilt - Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
18 | Huntsman Cancer Hospital | Salt Lake City | Utah | United States | 84112 |
19 | Huntsman Cancer Institute | Salt Lake City | Utah | United States | 84112 |
20 | Seattle Cancer Care Alliance (SCCA) | Seattle | Washington | United States | 98109 |
21 | University of Washington Medical Center (UWMC) | Seattle | Washington | United States | 98195 |
22 | Ziekenhuis Netwerk Antwerpen - Campus Stuivenberg | Antwerpen | Belgium | 2060 | |
23 | UZ Leuven | Leuven | Belgium | 3000 | |
24 | Tom Baker Cancer Center | Calgary | Alberta | Canada | T2N 4N2 |
25 | University Of Alberta Hospital | Edmonton | Alberta | Canada | T6G 2B7 |
26 | CHU d'Amiens-Picardie - Hopital SUD | Amiens cedex 01 | France | 80054 | |
27 | Hopital Saint-Louis (AP-HP) - Service Hematologie Senior | Paris CEDEX 10 | France | 75475 | |
28 | Hospices Civils de Lyon - Hopital Lyon Sud- Hematologie | Pierre Benite Cedex | France | 69495 | |
29 | CHU de Tours-Hopital Bretonneau-Centre Regional de cancerologie Henry Kaplan | Tours Cedex 01 | France | 37044 | |
30 | Staedtisches Klinikum Braunschweig gGmbH | Braunschweig | Germany | 38114 | |
31 | King's College Hospital | London | United Kingdom | SE5 9RS | |
32 | The Newcastle Hospitals NHS Foundation Trust | Newcastle upon Tyne | United Kingdom | NE7 7DN | |
33 | Oxford University Hospitals NHS Foundation Trust | Oxford | United Kingdom | OX3 9DU |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- B1371012
- 2014-001345-24
- BRIGHT MDS&AML1012
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 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 |
---|---|---|---|
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 |
Baseline Characteristics
Arm/Group Title | Lead-in Cohort | AML Cohort | MDS Cohort | Total |
---|---|---|---|---|
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 Participants | 12 | 30 | 30 | 72 |
Age, Customized (Count of Participants) | ||||
<18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
18-44 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
45-64 years |
3
25%
|
3
10%
|
7
23.3%
|
13
18.1%
|
>=65 years |
9
75%
|
27
90%
|
23
76.7%
|
59
81.9%
|
Age, Customized (Count of 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 (Count of Participants) | ||||
Female |
5
41.7%
|
12
40%
|
6
20%
|
23
31.9%
|
Male |
7
58.3%
|
18
60%
|
24
80%
|
49
68.1%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
0
0%
|
1
3.3%
|
2
6.7%
|
3
4.2%
|
Not Hispanic or Latino |
12
100%
|
23
76.7%
|
23
76.7%
|
58
80.6%
|
Unknown or Not Reported |
0
0%
|
6
20%
|
5
16.7%
|
11
15.3%
|
Race/Ethnicity, Customized (Count of Participants) | ||||
White |
11
91.7%
|
22
73.3%
|
24
80%
|
57
79.2%
|
Black or African American |
0
0%
|
1
3.3%
|
0
0%
|
1
1.4%
|
Asian |
1
8.3%
|
1
3.3%
|
0
0%
|
2
2.8%
|
Other |
0
0%
|
0
0%
|
1
3.3%
|
1
1.4%
|
Unknown |
0
0%
|
6
20%
|
5
16.7%
|
11
15.3%
|
Not reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) |
---|---|
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) |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
All-causality TEAEs |
12
100%
|
Treatment-related TEAEs |
12
100%
|
Maximum Grade 3 or 4 TEAEs |
8
66.7%
|
Title | Number of Participants With Serious Adverse Events (SAEs) in the LIC |
---|---|
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) |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
All-causality SAEs |
9
75%
|
Treatment-related SAEs |
7
58.3%
|
Title | Number of Participants With Laboratory Abnormalities in the LIC |
---|---|
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) |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
Activated partial thromboplastin time prolonged |
5
41.7%
|
Anemia |
12
100%
|
Hemoglobin increased |
0
0%
|
INR increased |
8
66.7%
|
Lymphocyte count decreased |
9
75%
|
Lymphocyte count increased |
3
25%
|
Neutrophil count decreased |
10
83.3%
|
Platelet count decreased |
12
100%
|
White blood cell decreased |
11
91.7%
|
Alanine aminotransferase increased |
4
33.3%
|
Alkaline phosphatase increase |
0
0%
|
Aspartate aminotransferase increased |
2
16.7%
|
Blood bilirubin increased |
6
50%
|
CPK increased |
0
0%
|
Creatinine increased |
11
91.7%
|
Hypercalcemia |
1
8.3%
|
Hyperglycemia |
1
8.3%
|
Hyperkalemia |
3
25%
|
Hypermagnesemia |
2
16.7%
|
Hypernatremia |
1
8.3%
|
Hypoalbuminemia |
5
41.7%
|
Hypocalcemia |
3
25%
|
Hypoglycemia |
1
8.3%
|
Hypokalemia |
3
25%
|
Hypomagnesemia |
2
16.7%
|
Hyponatremia |
6
50%
|
Hypophosphatemia |
4
33.3%
|
Title | Percentage of Participants Achieving Complete Remission (CR) in the AML and MDS Cohorts |
---|---|
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) |
Outcome Measure Data
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 |
---|---|---|
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. |
Measure Participants | 30 | 30 |
Number (95% Confidence Interval) [Percentage of participants] |
20.0
166.7%
|
13.3
44.3%
|
Title | Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC |
---|---|
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) |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
Number [Percentage of participants] |
25.0
208.3%
|
Title | Number of Participants With Efficacy Measures Other Than CR in the LIC |
---|---|
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) |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
Marrow CR (mCR) |
2
16.7%
|
Stable disease (SD) |
4
33.3%
|
Hematologic improvement (HI) of at least 1 lineage |
6
50%
|
Title | Number of Participants With TEAEs in the AML and MDS Cohorts |
---|---|
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) |
Outcome Measure Data
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 |
---|---|---|
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. |
Measure Participants | 30 | 30 |
All-causality TEAEs |
30
250%
|
30
100%
|
Treatment-related TEAEs |
29
241.7%
|
29
96.7%
|
Title | Number of Participants With SAEs in the AML and MDS Cohorts |
---|---|
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) |
Outcome Measure Data
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 |
---|---|---|
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. |
Measure Participants | 30 | 30 |
All-causality SAEs |
24
200%
|
18
60%
|
Treatment-related SAEs |
8
66.7%
|
8
26.7%
|
Title | Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts |
---|---|
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) |
Outcome Measure Data
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 |
---|---|---|
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. |
Measure Participants | 30 | 30 |
Activated partial thromboplastin time prolonged |
0
0%
|
0
0%
|
Anemia |
30
250%
|
29
96.7%
|
Hemoglobin increased |
0
0%
|
0
0%
|
INR increased |
0
0%
|
1
3.3%
|
Lymphocyte count decreased |
23
191.7%
|
23
76.7%
|
Lymphocyte count increased |
6
50%
|
1
3.3%
|
Neutrophil count decreased |
25
208.3%
|
25
83.3%
|
Platelet count decreased |
29
241.7%
|
26
86.7%
|
White blood cell decreased |
22
183.3%
|
27
90%
|
Alanine aminotransferase increased |
13
108.3%
|
12
40%
|
Alkaline phosphatase increased |
7
58.3%
|
7
23.3%
|
Aspartate aminotransferase increased |
11
91.7%
|
8
26.7%
|
Blood bilirubin increased |
3
25%
|
10
33.3%
|
CPK increased |
5
41.7%
|
4
13.3%
|
Creatinine increased |
29
241.7%
|
28
93.3%
|
Hypercalcemia |
3
25%
|
0
0%
|
Hyperglycemia |
3
25%
|
4
13.3%
|
Hyperkalemia |
6
50%
|
6
20%
|
Hypermagnesemia |
1
8.3%
|
2
6.7%
|
Hypernatremia |
2
16.7%
|
1
3.3%
|
Hypoalbuminemia |
22
183.3%
|
17
56.7%
|
Hypocalcemia |
3
25%
|
11
36.7%
|
Hypoglycemia |
4
33.3%
|
2
6.7%
|
Hypokalemia |
8
66.7%
|
3
10%
|
Hypomagnesemia |
12
100%
|
9
30%
|
Hyponatremia |
18
150%
|
12
40%
|
Hypophosphatemia |
13
108.3%
|
7
23.3%
|
Title | Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort |
---|---|
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) |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 30 |
CRh |
0
0%
|
CRi |
1
8.3%
|
PR |
2
16.7%
|
MLFS |
1
8.3%
|
SD |
6
50%
|
Title | Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort |
---|---|
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) |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 30 |
PR |
3
25%
|
mCR |
5
41.7%
|
SD |
8
66.7%
|
Complete cytogenetic response |
3
25%
|
Partial cytogenetic response |
1
8.3%
|
HI of at least 1 lineage |
9
75%
|
HI of at least 1 lineage without CR or PR |
3
25%
|
Title | Kaplan-Meier Estimate of Median Overall Survival (OS) in the AML and MDS Cohorts |
---|---|
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) |
Outcome Measure Data
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 |
---|---|---|
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. |
Measure Participants | 30 | 30 |
Median (95% Confidence Interval) [Months] |
9.2
|
15.8
|
Title | Duration of CR in the AML and MDS Cohorts |
---|---|
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) |
Outcome Measure Data
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 |
---|---|---|
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. |
Measure Participants | 30 | 30 |
Median (Full Range) [Months] |
4.73
|
3.71
|
Title | Time to CR in the AML and MDS Cohorts |
---|---|
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) |
Outcome Measure Data
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 |
---|---|---|
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. |
Measure Participants | 30 | 30 |
Median (Full Range) [Months] |
5.54
|
4.39
|
Title | Maximum Plasma Concentration (Cmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort |
---|---|
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 |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
C1D7 |
1013
(58)
|
C1D15 |
991.4
(57)
|
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 |
---|---|
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 |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
C1D7 |
13230
(49)
|
C1D15 |
14350
(61)
|
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 |
---|---|
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 |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
C1D7 |
1.050
|
C1D15 |
1.500
|
Title | Maximum Plasma Concentration (Cmax) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort |
---|---|
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. |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
C1D1 |
778.5
(23)
|
C1D7 |
716.9
(32)
|
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 |
---|---|
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. |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
C1D1 |
1319
(19)
|
C1D7 |
1260
(21)
|
Title | Tmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort |
---|---|
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. |
Outcome Measure Data
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 |
---|---|
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. |
Measure Participants | 12 |
C1D1 |
0.5000
|
C1D7 |
0.5000
|
Title | Trough Plasma Concentration (Ctrough) of Glasdegib on C1D15 and C2D1 in the AML and MDS Cohorts |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|
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. |
Measure Participants | 30 | 30 |
C1D15 |
468.440
(88)
|
308.144
(95)
|
C2D1 |
462.806
(110)
|
167.483
(52)
|
Title | Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts |
---|---|
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) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Lead-in Cohort | AML Cohort | MDS Cohort |
---|---|---|---|
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. |
Measure Participants | 12 | 30 | 30 |
Maximum QTcF interval <450 ms |
5
41.7%
|
16
53.3%
|
18
60%
|
450 ms <=Maximum QTcF interval <480 ms |
2
16.7%
|
6
20%
|
6
20%
|
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%
|
2
6.7%
|
QTcF maximum increase from baseline <30 ms |
3
25%
|
18
60%
|
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%
|
Adverse Events
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 | |||
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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 9/12 (75%) | 22/30 (73.3%) | 15/30 (50%) | |||
Serious Adverse Events |
||||||
Lead-in Cohort | AML Cohort | MDS Cohort | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 9/12 (75%) | 24/30 (80%) | 18/30 (60%) | |||
Blood and lymphatic system disorders | ||||||
Anaemia | 0/12 (0%) | 1/30 (3.3%) | 1/30 (3.3%) | |||
Febrile neutropenia | 4/12 (33.3%) | 6/30 (20%) | 5/30 (16.7%) | |||
Thrombocytopenia | 0/12 (0%) | 1/30 (3.3%) | 1/30 (3.3%) | |||
Cardiac disorders | ||||||
Acute myocardial infarction | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Angina pectoris | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Atrial fibrillation | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Cardiac failure | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Right ventricular failure | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Gastrointestinal disorders | ||||||
Abdominal pain | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Ascites | 0/12 (0%) | 1/30 (3.3%) | 1/30 (3.3%) | |||
Constipation | 1/12 (8.3%) | 1/30 (3.3%) | 0/30 (0%) | |||
Gastrointestinal haemorrhage | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Nausea | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Upper gastrointestinal haemorrhage | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Vomiting | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
General disorders | ||||||
Disease progression | 0/12 (0%) | 3/30 (10%) | 1/30 (3.3%) | |||
General physical health deterioration | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Multiple organ dysfunction syndrome | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Pyrexia | 2/12 (16.7%) | 4/30 (13.3%) | 2/30 (6.7%) | |||
Infections and infestations | ||||||
Bacteraemia | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Bronchopulmonary aspergillosis | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Catheter site cellulitis | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Cellulitis | 2/12 (16.7%) | 0/30 (0%) | 1/30 (3.3%) | |||
Cystitis | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Lower respiratory tract infection | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Neutropenic sepsis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Osteomyelitis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Pneumonia | 0/12 (0%) | 1/30 (3.3%) | 1/30 (3.3%) | |||
Pseudomonal sepsis | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Pyelonephritis | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Respiratory tract infection | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Sepsis | 0/12 (0%) | 1/30 (3.3%) | 5/30 (16.7%) | |||
Septic shock | 1/12 (8.3%) | 1/30 (3.3%) | 0/30 (0%) | |||
Streptococcal infection | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Urinary tract infection | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Urosepsis | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Injury, poisoning and procedural complications | ||||||
Fall | 0/12 (0%) | 1/30 (3.3%) | 1/30 (3.3%) | |||
Femur fracture | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Lumbar vertebral fracture | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Post procedural haemorrhage | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Sternal fracture | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Subdural haematoma | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Investigations | ||||||
Electrocardiogram QT prolonged | 1/12 (8.3%) | 2/30 (6.7%) | 0/30 (0%) | |||
Metabolism and nutrition disorders | ||||||
Gout | 1/12 (8.3%) | 0/30 (0%) | 1/30 (3.3%) | |||
Hyponatraemia | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Tumor lysis syndrome | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Arthralgia | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Musculoskeletal chest pain | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Gastrointestinal lymphoma | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Lung neoplasm malignant | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Metastases to liver | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Myelodysplastic syndrome | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Nervous system disorders | ||||||
Cerebral haemorrhage | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Cerebrovascular accident | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Subarachnoid haemorrhage | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Syncope | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Psychiatric disorders | ||||||
Depression | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Renal and urinary disorders | ||||||
Acute kidney injury | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Renal failure | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Acute respiratory distress syndome | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Epistaxis | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Hypoxia | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Pneumonitis | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Pulmonary arterial hypertension | 0/12 (0%) | 0/30 (0%) | 1/30 (3.3%) | |||
Respiratory failure | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Vascular disorders | ||||||
Haematoma | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Hypotension | 0/12 (0%) | 1/30 (3.3%) | 1/30 (3.3%) | |||
Orthostatic hypotension | 0/12 (0%) | 1/30 (3.3%) | 0/30 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Lead-in Cohort | AML Cohort | MDS Cohort | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 12/12 (100%) | 29/30 (96.7%) | 29/30 (96.7%) | |||
Blood and lymphatic system disorders | ||||||
Anaemia | 9/12 (75%) | 6/30 (20%) | 11/30 (36.7%) | |||
Febrile neutropenia | 0/12 (0%) | 3/30 (10%) | 2/30 (6.7%) | |||
Leukopenia | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Neutropenia | 6/12 (50%) | 0/30 (0%) | 3/30 (10%) | |||
Thrombocytopenia | 3/12 (25%) | 0/30 (0%) | 3/30 (10%) | |||
Cardiac disorders | ||||||
Atrial fibrillation | 0/12 (0%) | 2/30 (6.7%) | 3/30 (10%) | |||
Tachycardia | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Ear and labyrinth disorders | ||||||
Ear pain | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Tinnitus | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Eye disorders | ||||||
Vision blurred | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Gastrointestinal disorders | ||||||
Abdominal pain | 2/12 (16.7%) | 6/30 (20%) | 4/30 (13.3%) | |||
Abdominal pain upper | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Ascites | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Constipation | 9/12 (75%) | 18/30 (60%) | 15/30 (50%) | |||
Dental caries | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Diarrhoea | 6/12 (50%) | 16/30 (53.3%) | 14/30 (46.7%) | |||
Dry mouth | 2/12 (16.7%) | 4/30 (13.3%) | 4/30 (13.3%) | |||
Dysepsia | 2/12 (16.7%) | 0/30 (0%) | 2/30 (6.7%) | |||
Dysphagia | 0/12 (0%) | 0/30 (0%) | 3/30 (10%) | |||
Enterocolitis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Gastrooesophageal reflux disease | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Gingival bleeding | 1/12 (8.3%) | 0/30 (0%) | 2/30 (6.7%) | |||
Haematochezia | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Haemorrhoids | 1/12 (8.3%) | 4/30 (13.3%) | 2/30 (6.7%) | |||
Nausea | 8/12 (66.7%) | 19/30 (63.3%) | 20/30 (66.7%) | |||
Oesophagitis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Oral dysaethesia | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Proctalgia | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Rectal haemorrhage | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Stomatitis | 1/12 (8.3%) | 2/30 (6.7%) | 4/30 (13.3%) | |||
Vomiting | 4/12 (33.3%) | 13/30 (43.3%) | 10/30 (33.3%) | |||
General disorders | ||||||
Asthenia | 2/12 (16.7%) | 3/30 (10%) | 0/30 (0%) | |||
Chest pain | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Chills | 1/12 (8.3%) | 2/30 (6.7%) | 0/30 (0%) | |||
Fatigue | 6/12 (50%) | 8/30 (26.7%) | 9/30 (30%) | |||
General physical health deterioration | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Injection site erythema | 3/12 (25%) | 2/30 (6.7%) | 0/30 (0%) | |||
Injection site irritation | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Injection site nodule | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Injection site pain | 0/12 (0%) | 3/30 (10%) | 0/30 (0%) | |||
Injection site reaction | 2/12 (16.7%) | 2/30 (6.7%) | 5/30 (16.7%) | |||
Oedema peripheral | 3/12 (25%) | 4/30 (13.3%) | 8/30 (26.7%) | |||
Pain | 1/12 (8.3%) | 5/30 (16.7%) | 2/30 (6.7%) | |||
Pyrexia | 2/12 (16.7%) | 8/30 (26.7%) | 3/30 (10%) | |||
Hepatobiliary disorders | ||||||
Ischaemic hepatitis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Jaundice | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Infections and infestations | ||||||
Bacteraemia | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Cellulitis | 2/12 (16.7%) | 0/30 (0%) | 0/30 (0%) | |||
Device related infection | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Diverticulitis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Folliculitis | 3/12 (25%) | 0/30 (0%) | 0/30 (0%) | |||
Oral candidiasis | 0/12 (0%) | 4/30 (13.3%) | 0/30 (0%) | |||
Pneumonia | 3/12 (25%) | 0/30 (0%) | 2/30 (6.7%) | |||
Sepsis | 2/12 (16.7%) | 0/30 (0%) | 0/30 (0%) | |||
Sinusitis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Upper respiratory tract infection | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Urinary tract infection | 3/12 (25%) | 2/30 (6.7%) | 2/30 (6.7%) | |||
Injury, poisoning and procedural complications | ||||||
Contusion | 2/12 (16.7%) | 0/30 (0%) | 5/30 (16.7%) | |||
Fall | 0/12 (0%) | 8/30 (26.7%) | 7/30 (23.3%) | |||
Postoperative hypotension | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Investigations | ||||||
Alanine transferase increased | 0/12 (0%) | 3/30 (10%) | 4/30 (13.3%) | |||
Aspartate aminotransferase increase | 0/12 (0%) | 4/30 (13.3%) | 5/30 (16.7%) | |||
Blood alkaline phosphatase increased | 0/12 (0%) | 3/30 (10%) | 2/30 (6.7%) | |||
Blood bilirubin increased | 2/12 (16.7%) | 3/30 (10%) | 4/30 (13.3%) | |||
Blood creatine phosphokinase increased | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Blood creatinine increased | 0/12 (0%) | 4/30 (13.3%) | 4/30 (13.3%) | |||
Blood lactate dehydrogenase increased | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
C-reactive protein increased | 0/12 (0%) | 3/30 (10%) | 0/30 (0%) | |||
Electrocardiogram QT prolonged | 5/12 (41.7%) | 5/30 (16.7%) | 3/30 (10%) | |||
Heart rate irregular | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
International normalised ratio increased | 0/12 (0%) | 3/30 (10%) | 2/30 (6.7%) | |||
Lymphocyte count decreased | 0/12 (0%) | 4/30 (13.3%) | 4/30 (13.3%) | |||
Neutrophil count decreased | 0/12 (0%) | 2/30 (6.7%) | 11/30 (36.7%) | |||
Platelet count decreased | 0/12 (0%) | 5/30 (16.7%) | 11/30 (36.7%) | |||
Weight decreased | 5/12 (41.7%) | 4/30 (13.3%) | 5/30 (16.7%) | |||
White blood cell count decreased | 1/12 (8.3%) | 7/30 (23.3%) | 8/30 (26.7%) | |||
Metabolism and nutrition disorders | ||||||
Decreased appetite | 2/12 (16.7%) | 16/30 (53.3%) | 9/30 (30%) | |||
Hyperglycaemia | 0/12 (0%) | 4/30 (13.3%) | 6/30 (20%) | |||
Hyperkalaemia | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Hypernatraemia | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Hyperuricaemia | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Hypoalbuminaemia | 0/12 (0%) | 5/30 (16.7%) | 4/30 (13.3%) | |||
Hypocalcaemia | 1/12 (8.3%) | 2/30 (6.7%) | 0/30 (0%) | |||
Hypokalaemia | 1/12 (8.3%) | 8/30 (26.7%) | 2/30 (6.7%) | |||
Hypomagnesaemia | 2/12 (16.7%) | 6/30 (20%) | 6/30 (20%) | |||
Hyponatraemia | 3/12 (25%) | 7/30 (23.3%) | 6/30 (20%) | |||
Hypophosphataemia | 2/12 (16.7%) | 2/30 (6.7%) | 2/30 (6.7%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Arthralgia | 0/12 (0%) | 2/30 (6.7%) | 3/30 (10%) | |||
Arthritis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Back pain | 0/12 (0%) | 6/30 (20%) | 0/30 (0%) | |||
Flank pain | 0/12 (0%) | 3/30 (10%) | 2/30 (6.7%) | |||
Haemarthrosis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Muscle spasms | 4/12 (33.3%) | 9/30 (30%) | 15/30 (50%) | |||
Muscular weakness | 0/12 (0%) | 4/30 (13.3%) | 4/30 (13.3%) | |||
Myalgia | 1/12 (8.3%) | 2/30 (6.7%) | 5/30 (16.7%) | |||
Neck pain | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Pain in extremity | 2/12 (16.7%) | 0/30 (0%) | 0/30 (0%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Melanocytic naevus | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Nervous system disorders | ||||||
Ageusia | 0/12 (0%) | 2/30 (6.7%) | 2/30 (6.7%) | |||
Amnesia | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Dizziness | 2/12 (16.7%) | 3/30 (10%) | 7/30 (23.3%) | |||
Dizziness postural | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Dysgeusia | 5/12 (41.7%) | 4/30 (13.3%) | 13/30 (43.3%) | |||
Headache | 0/12 (0%) | 3/30 (10%) | 7/30 (23.3%) | |||
Hypoaesthesia | 1/12 (8.3%) | 0/30 (0%) | 3/30 (10%) | |||
Hypogeusia | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Paraesthesia | 0/12 (0%) | 4/30 (13.3%) | 0/30 (0%) | |||
Presyncope | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Taste disorder | 1/12 (8.3%) | 3/30 (10%) | 0/30 (0%) | |||
Psychiatric disorders | ||||||
Anxiety | 1/12 (8.3%) | 4/30 (13.3%) | 0/30 (0%) | |||
Delirium | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Depression | 1/12 (8.3%) | 0/30 (0%) | 2/30 (6.7%) | |||
Insomnia | 2/12 (16.7%) | 6/30 (20%) | 5/30 (16.7%) | |||
Mental status change | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Sleep disorder | 0/12 (0%) | 3/30 (10%) | 3/30 (10%) | |||
Renal and urinary disorders | ||||||
Acute kidney injury | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Dysuria | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Haematuria | 2/12 (16.7%) | 2/30 (6.7%) | 0/30 (0%) | |||
Pollakiuria | 3/12 (25%) | 0/30 (0%) | 2/30 (6.7%) | |||
Renal failure | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Urinary incontinence | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Urinary retention | 2/12 (16.7%) | 0/30 (0%) | 0/30 (0%) | |||
Urinary tract pain | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Atelectasis | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Cough | 3/12 (25%) | 7/30 (23.3%) | 5/30 (16.7%) | |||
Dysphonia | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Dyspnoea | 4/12 (33.3%) | 8/30 (26.7%) | 6/30 (20%) | |||
Dyspnoea exertional | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Epistaxis | 1/12 (8.3%) | 4/30 (13.3%) | 4/30 (13.3%) | |||
Hiccups | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Hypoxia | 2/12 (16.7%) | 0/30 (0%) | 0/30 (0%) | |||
Nasal congestion | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Oropharyngeal pain | 2/12 (16.7%) | 4/30 (13.3%) | 0/30 (0%) | |||
Pleural effusion | 1/12 (8.3%) | 3/30 (10%) | 0/30 (0%) | |||
Respiratory distress | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Rhinorrhoea | 4/12 (33.3%) | 2/30 (6.7%) | 2/30 (6.7%) | |||
Tachypnoea | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Skin and subcutaneous tissue disorders | ||||||
Acne | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Alopecia | 4/12 (33.3%) | 2/30 (6.7%) | 7/30 (23.3%) | |||
Dermatitis acneiform | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Ecchymosis | 2/12 (16.7%) | 0/30 (0%) | 0/30 (0%) | |||
Erythema | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Night sweats | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Pruitus | 1/12 (8.3%) | 0/30 (0%) | 2/30 (6.7%) | |||
Purpura | 0/12 (0%) | 0/30 (0%) | 3/30 (10%) | |||
Rash | 3/12 (25%) | 3/30 (10%) | 3/30 (10%) | |||
Rash maculo-papular | 0/12 (0%) | 0/30 (0%) | 2/30 (6.7%) | |||
Skin disorder | 0/12 (0%) | 2/30 (6.7%) | 0/30 (0%) | |||
Skin ulcer | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Vascular disorders | ||||||
Deep vein thrombosis | 0/12 (0%) | 3/30 (10%) | 0/30 (0%) | |||
Haematoma | 2/12 (16.7%) | 3/30 (10%) | 0/30 (0%) | |||
Haemorrhage | 1/12 (8.3%) | 0/30 (0%) | 0/30 (0%) | |||
Hypertension | 0/12 (0%) | 3/30 (10%) | 0/30 (0%) | |||
Hypotension | 2/12 (16.7%) | 3/30 (10%) | 8/30 (26.7%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
Name/Title | Pfizer ClinicalTrials.gov Call Center |
---|---|
Organization | Pfizer, Inc. |
Phone | 8007181021 |
ClinicalTrials.gov_Inquiries@pfizer.com |
- B1371012
- 2014-001345-24
- BRIGHT MDS&AML1012