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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01546038
First received: March 1, 2012
Last updated: July 10, 2014
Last verified: July 2014

March 1, 2012
July 10, 2014
July 2012
November 2015   (final data collection date for primary outcome measure)
  • Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: 1 -year ] [ Designated as safety issue: Yes ]
    (Phase 1B)
  • Percentage of patients with Complete Response rate [ Time Frame: 2-years ] [ Designated as safety issue: No ]
    Complete response are those with repeat bone marrow showing less than 5 percent (%) myeloblasts with normal peripheral blood values. (Phase 2 Fit)
  • Overall Survival (OS) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Time from the start of study treatment to date of death due to any cause. (Phase 2 Unfit)
  • First cycle dose limiting toxicities [ Time Frame: 1 -year ] [ Designated as safety issue: Yes ]
  • Complete Response [ Time Frame: 2-years ] [ Designated as safety issue: No ]
  • Complete Response with Incomplete Blood count Recovery [ Time Frame: 2-years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01546038 on ClinicalTrials.gov Archive Site
  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Not Specified (Phase 1B; Phase 2 Fit and Unfit)
  • Overall Survival (OS) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Time from the start of study treatment to date of death due to any cause. (Phase 1B; Phase 2 Fit)
  • Percentage of patients with disease-specific efficacy for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (Phase 2 Fit and Unfit)
  • Percentage of patients with Complete Response rate / Complete Response rate with incomplete blood count recovery [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Complete response are those with repeat bone marrow showing less than 5 percent (%) myeloblasts with normal peripheral blood values. (Phase 1B; Phase 2 Unfit); Complete response with incomplete blood count recovery are those with repeat bone marrow showing less than 5 percent (%) myeloblasts with either platelets or neutrophils not recovered.
  • Cumulative incidence of relapse (CIR), relapse free survival (RFS), event free survival (EFS), and cumulative incidence of death (CID) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    RFS, CIR and CID are defined only for patients achieving CR or CRi (Phase 2 Fit and Unfit); EFS (P2 Fit only) is defined as the time from C1D-3 to date of induction treatment failure, or relapse from CR or CRi, or death from any cause.
  • QTc Interval [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    (Phase 1B; Phase 2 Fit and Unfit)
  • Disease-related gene mutation (PD biomarkers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (Phase 1B; Phase 2 Fit and Unfit)
  • Changes in analyte levels from baseline to post-treatment (PD biomarkers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (Phase 1B; Phase 2 Fit and Unfit)
  • Changes in gene levels from baseline to post-treatment (PD biomarkers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (Phase 1B; Phase 2 Fit and Unfit)
  • Detectable tumor Gli1 expression (PD Biomarkers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (Phase 1B; Phase 2 Fit and Unfit)
  • Area under the plasma concentration versus time curve (AUC) of all study drugs [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Peak Plasma Concentration (Cmax) of all study drugs [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Cumulative Incidence of Relapse [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Relapse Free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Event free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Cumulative incidence of Death [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • QTc Interval [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
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

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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Myeloid Leukemia
  • Drug: PF-04449913
    PF-04449913 administered orally and continuously for 28-days.
  • Drug: Low dose ARA-C (LDAC)
    Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.
  • Drug: PF-04449913
    PF-04449913 administered orally and continuously for 28 days.
  • Drug: Decitabine
    Decitabine given at 20 mg/m2 over 1 hour infusion for 5-days
  • Drug: PF-04449913
    PF-04449913 administered orally and continuously for 28 days
  • Drug: Daunorubicin
    Daunorubicin given using 60 mg/m2 for 3-days
  • Drug: Cytarabine
    Cytarabine 100 mg/m2 on days 1 through 7
  • Drug: Pf-04449913
    PF-04449913 administered orally and continuously for 28 days
  • Drug: PF-04449913
    PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913)
  • Experimental: Arm A (Phase 1B)
    PF-04449913 in combination with low dose ARA-C (LDAC)
    Interventions:
    • Drug: PF-04449913
    • Drug: Low dose ARA-C (LDAC)
  • Experimental: Arm B (Phase 1B)
    PF-04449913 in combination with Decitabine
    Interventions:
    • Drug: PF-04449913
    • Drug: Decitabine
  • Experimental: Arm C (Phase 1B)
    PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.
    Interventions:
    • Drug: PF-04449913
    • Drug: Daunorubicin
    • Drug: Cytarabine
  • Experimental: P2 Fit (Phase 2 Single Arm)
    PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.
    Interventions:
    • Drug: Pf-04449913
    • Drug: Daunorubicin
    • Drug: Cytarabine
  • P2 Unfit (Phase 2 Randomized)
    Patients will be randomized 2:1 (low dose ARA-C in combination with PF-04449913: low dose ARA-C alone).
    Interventions:
    • Drug: PF-04449913
    • Drug: Low dose ARA-C (LDAC)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
265
November 2015
November 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with AML or RAEB 2 High Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated.
  • Patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML.
  • AML patients include de novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML)
  • For a diagnosis of AML, a bone marrow blast count of 20% or more is required.
  • For a diagnosis of high-risk Myelodysplastic Syndrome RAEB 2 the patient must have 10-19% bone marrow blasts
  • Adequate Organ Function
  • ECOG Performance Status 0, 1, or 2

Exclusion Criteria:

  • AML M3 Acute Promyelocytic Leukemia (APL) or patients with a t(9:22) cytogenetic translocation.
  • Patients in whom, at the time of study entry, a stem cell transplant is planned within the next 6 months.
  • Patients with known active uncontrolled central nervous system (CNS) leukemia.
Both
18 Years and older
No
Contact: Pfizer CT.gov Call Center 1-800-718-1021
United States,   Canada,   Italy,   Poland,   Spain
 
NCT01546038
B1371003
Yes
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP