A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

Official Title

A Phase 1b/2 Study To Evaluate The Safety And Efficacy Of Pf-04449913, An Oral Hedgehog Inhibitor, In Combination With Intensive Chemotherapy, Low Dose Ara-c Or Decitabine In Patients With Acute Myeloid Leukemia Or High-risk Myelodysplastic Syndrome

Summary:

This is a study to evaluate PF-04449913 (an inhibitor of the Hedgehog pathway) in Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome in combination with standard agents used to treat these diseases.

Trial Description

Primary Outcome:

  • Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
  • Percentage of Participants With Complete Response (CR) at Phase 2 Fit
  • Overall Survival (OS) at Phase 2 Unfit
Secondary Outcome:
  • Overall Survival (OS) at Phase 1B
  • Overall Survival (OS) at Phase 2 Fit
  • Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B
  • Percentage of Participants With Complete Response (CR) at Phase 2 Unfit
  • Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
  • Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
  • Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
  • Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
  • Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
  • Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
  • Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
  • AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
  • Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
  • Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
  • AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
  • Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
  • Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
  • Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
  • Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
  • Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
  • Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
  • AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
  • AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
  • Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
  • Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
  • AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
  • Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10
  • Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
  • Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
  • AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
  • Number of Participants With Disease-related Gene Mutations at Phase 1B
  • Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline
  • Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3
  • Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10
  • Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B
  • Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In
  • Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3
  • Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit
  • Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3
  • Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10
  • Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1
  • Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10
  • Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment
  • Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit
  • Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3
  • Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10
  • Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment
  • Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1
  • Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10
  • Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit
  • Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1
  • Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment
  • Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3
  • Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment
  • Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment
  • Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit
  • Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
  • Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit
  • Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
  • Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B
  • Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit
  • Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)
  • Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)
  • Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B
  • Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)
  • Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)
  • Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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