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

• ClinicalTrials.gov Identifier: NCT02367456
• Recruitment Status: Active, not recruiting
• First Posted: February 20, 2015
• Results First Posted: March 5, 2021
• Last Update Posted: November 8, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: February 13, 2015
• First Posted Date: February 20, 2015
• Results First Submitted Date: January 19, 2021
• Results First Posted Date: March 5, 2021
• Last Update Posted Date: November 8, 2021
• Actual Study Start Date: April 28, 2015
• Actual Primary Completion Date: January 29, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2021)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) [ 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) ]
  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 [ 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) ]
  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 [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 13, 2015)

RR (hematology) [ Time Frame: All cycles up until 30 months from randomization ]

Response rate (percentage of patients achieving CR + PR) as defined by modified IWG criteria (2006) (Phase 2)

Current Secondary Outcome Measures (submitted: March 4, 2021)

• Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ 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. ]
  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 [ 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. ]
  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 [ 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. ]
  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 [ Time Frame: 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 [ 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) ]
  Number of participants that met categorical criteria of QTcF values in LIC, AML and MDS cohorts

Original Secondary Outcome Measures (submitted: February 13, 2015)

• RR(Hematology) [ Time Frame: All Cycles up until 30 months from randomization ]
  Response Rate - (Percentage of Participants achieving CR + PR) as defined by modified IWG criteria (2006)(Phase 1)
• Hematologic Improvement [ Time Frame: All cycles up until 30 months from randomization ]
  Hematologic Improvement, as defined by modified IWG (2006) (Phase 1).
• Marrow Complete Response (mCR) [ Time Frame: All cycles up until 30 months from randomization ]
  Marrow Complete Response, as defined by modified IWG (2006) (Phase 1).
• Cytogenetic Response [ Time Frame: All cycles up until 30 months from randomization ]
  Cytogenic Response as defined by modified IWG (2006) (Phase 1).
• Transfusion Independence [ Time Frame: All cycles up until 30 months from randomization ]
  Proportion of patients becoming transfusion independent on study in patients who were transfusion dependent at the time of study entry (Phase 1).
• Stable Disease [ Time Frame: All cycles up until 30 months from randomization ]
  Stable Disease as defined by modified IWG (2006) (Phase 1).
• QTc interval [ Time Frame: Cycle 1 through Cycle 6 and End of Treatment up until 30 months from randomization ]
  QTc interval corrected using Fridericia's Formula (msec) (Phase 1)
• AUC for PF-04449913 [ Time Frame: 0. .25, .5, 1, 2, 4, 6, and 24 hours post-dose ]
  Area under the Concentration-Time Curve (ng*h/mL) (Phase 1).
• Cmax for PF-04449913 [ Time Frame: 0, .25, .5, 1, 2, 4, 6, and 24 hours post-dose ]
  Maximum Observed Plasma Concentration (ng/mL) (Phase 1).
• Tmax for PF-04449913 [ Time Frame: 0, .25, .5, 1, 2, 4, 6, and 24 hours post-dose ]
  Time to Reach Maximum Observed Plasma Concentration (hrs) (Phase 1).
• AUC for Azacitidine [ Time Frame: 0, .25, .5, 1, 2, and 6 hours post-dose ]
  Area under the Concentration-Time Curve (ng*h/mL) (Phase 1).
• Cmax for Azacitidine [ Time Frame: 0, .25, .5, 1, 2, and 6 hours post-dose ]
  Maximum Observed Plasma Concentration (ng/mL) (Phase 1).
• Tmax for Azacitidine [ Time Frame: 0, .25, .5, 1, 2 and 6 hours post-dose ]
  Time to Reach Maximum Observed Plasma Concentration (hrs) (Phase 1).
• Duration of Hematologic Improvement (HI) [ Time Frame: All cycles until disease progression or up until 30 months from randomization ]
  Duration of HI defined as time from start of first documented HI to first documented disease progression or relapse after HI or death due to any cause, whichever occurs first (Phase 2).
• Time to Best Response or any hematologic improvement [ Time Frame: All cycles up until 30 months from randomization ]
  Time from randomization to achieving best response CR, PR or any HI. (Phase 2 only).
• Survival: Probability of Participant Survival [ Time Frame: 12, 18 and 24 months ]
  Probability of survival at 12, 18 and 24 months after randomization (Phase 2).
• Hematologic Improvement [ Time Frame: All cycles up until 30 months from randomization ]
  Hematologic Improvement, as defined by modified IWG (2006) (Phase 2).
• Transfusion independence [ Time Frame: All cycles up until 30 months from randomization ]
  Proportion of patients becoming transfusion independent on study in patients who were transfusion dependent at the time of study entry (Phase 2).
• QTc interval [ Time Frame: Cycle 1 through Cycle 6 and End of Treatment up until 30 months from randomization ]
  QTc interval corrected using Fridericia's Formula (msec) (Phase 2)
• Marrow Complete Response (mCR) [ Time Frame: All cycles up until 30 months from randomization ]
  Marrow Complete Response, as defined by modified IWG (2006) (Phase 2).
• Cytogenic Response [ Time Frame: All cycles up until 30 months from randomization ]
  Cytogenic Response as defined by modified IWG (2006) (Phase 2).
• Stable Disease [ Time Frame: All cycles up until 30 months from randomization ]
  Stable Disease as defined by modified IWG (2006) (Phase 2).
• Duration of Response [ Time Frame: All cycles until progression or up until 30 months from randomization ]
  Duration of response (DR) defined as time from start of first documented disease response [Complete Response (CR) or Partial Response (PR)] to first documented disease progression or death due to any cause, whichever occurs first (Phase 2).
• Time to First Response or any hematologic improvement [ Time Frame: All cycles up until 30 months from randomization ]
  Time from randomization to first achieving CR, PR or HI (Phase 2).
• Time to reaching >30% bone marrow blasts [ Time Frame: All cycles up unitl 30 months from randomization ]
  From Randomization to first reaching >30% bone marrow blasts (Phase 2).
• Ctrough [ Time Frame: Cycle 1 Day 15 and Cycle 2 Day 1 ]
  Minimum Observed Plasma Trough Concentration (ng/mL)(Phase 2).
• Overal Survival (OS) [ Time Frame: Randomization till death up until 30 months from randomization ]
  Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact (Phase 2).
• Event Free Survival [ Time Frame: All Cycles up until 30 months from randomization ]
  Time from Randomization to first documentation of bone marrow blasts >30% or death for any reason whichever occurs first (Phase 2).
• EQ-5D [ Time Frame: Baseline and Every Cycle up until 30 months from randomization ]
  Change From Baseline in Euro Quality of Life - Health State Profile Utility, Visual Analog Scale (VAS), and Dimension Health State EuroQol Score at Every Cycle (Phase 2).
• EORTC-QLQ-C30 [ Time Frame: Baseline and Every Cycle up until 30 months from randomization ]
  European Organization of Research and the Treatment of Cancer- Quality of Life Core Questionnaire (Phase 2)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients
• Official Title: AN OPEN-LABEL PHASE 1B STUDY OF PF-04449913 (GLASDEGIB) IN COMBINATION WITH AZACITIDINE IN PATIENTS WITH PREVIOUSLY UNTREATED HIGHER-RISK MYELODYSPLASTIC SYNDROME, ACUTE MYELOID LEUKEMIA, OR CHRONIC MYELOMONOCYTIC LEUKEMIA
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Myelodysplastic Syndrome
• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia

Intervention

• 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

Study Arms

• Experimental: Arm A
  MDS patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2
  Interventions:

  • Drug: PF-04449913 (Glasdegib)
  • Drug: Azacitidine
• Experimental: Arm B
  AML patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2
  Interventions:

  • Drug: PF-04449913 (Glasdegib)
  • Drug: Azacitidine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 9, 2019): 73
• Original Estimated Enrollment (submitted: February 13, 2015): 170
• Estimated Study Completion Date: December 21, 2021
• Actual Primary Completion Date: January 29, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, France, Germany, United Kingdom, United States
• Removed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT02367456
• Other Study ID Numbers: B1371012; 2014-001345-24 ( EudraCT Number ); BRIGHT MDS&AML1012 ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2021