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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
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: PF-04449913
Drug: Low dose ARA-C (LDAC)
Drug: Decitabine
Drug: Daunorubicin
Drug: Cytarabine
Drug: Pf-04449913
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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)


Estimated Enrollment: 265
Study Start Date: July 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (Phase 1B)
PF-04449913 in combination with low dose ARA-C (LDAC)
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.
Experimental: Arm B (Phase 1B)
PF-04449913 in combination with Decitabine
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
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.
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
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.
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
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).
Drug: PF-04449913
PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913)
Drug: Low dose ARA-C (LDAC)
Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01546038

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

  Show 53 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01546038     History of Changes
Other Study ID Numbers: B1371003
Study First Received: March 1, 2012
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Hedgehog Inhibitor
Acute Myeloid Leukemia
Myelodysplastic syndrome
Intensive chemotherapy
LDAC

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Decitabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014