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 September 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01546038
First received: March 1, 2012
Last updated: September 9, 2014
Last verified: September 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
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: September 2016
Estimated Primary Completion Date: September 2016 (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 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

  Hide Study Locations
Locations
United States, Alabama
Pfizer Investigational Site Recruiting
Birmingham, Alabama, United States, 35249
Pfizer Investigational Site Recruiting
Birmingham, Alabama, United States, 35294
Pfizer Investigational Site Recruiting
Birmingham, Alabama, United States, 35249-6909
Pfizer Investigational Site Recruiting
Birmingham, Alabama, United States, 35233
United States, California
Pfizer Investigational Site Recruiting
Carlsbad, California, United States, 92008
Pfizer Investigational Site Recruiting
La Jolla, California, United States, 92093
Pfizer Investigational Site Recruiting
Los Angeles, California, United States, 90095
Pfizer Investigational Site Recruiting
Los Angeles, California, United States, 90033
United States, Colorado
Pfizer Investigational Site Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Pfizer Investigational Site Recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Pfizer Investigational Site Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Pfizer Investigational Site Recruiting
Chicago, Illinois, United States, 60611
Pfizer Investigational Site Recruiting
Chicago, Illinois, United States, 60637
United States, Indiana
Pfizer Investigational Site Recruiting
Indianapolis, Indiana, United States, 46214
United States, Kansas
Pfizer Investigational Site Recruiting
Fairway, Kansas, United States, 66205
Pfizer Investigational Site Recruiting
Kansas City, Kansas, United States, 66160
Pfizer Investigational Site Recruiting
Westwood, Kansas, United States, 66205
United States, Maryland
Pfizer Investigational Site Recruiting
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Pfizer Investigational Site Recruiting
Boston, Massachusetts, United States, 02114
Pfizer Investigational Site Recruiting
Boston, Massachusetts, United States, 02115
Pfizer Investigational Site Recruiting
Boston, Massachusetts, United States, 02215
Pfizer Investigational Site Recruiting
Boston, Massachusetts, United States, 02111
United States, Michigan
Pfizer Investigational Site Recruiting
Ann Arbor, Michigan, United States, 48109
Pfizer Investigational Site Recruiting
Detroit, Michigan, United States, 48201
Pfizer Investigational Site Recruiting
Farmington Hills, Michigan, United States, 48334
United States, Missouri
Pfizer Investigational Site Recruiting
Creve Coeur, Missouri, United States, 63141
Pfizer Investigational Site Recruiting
Saint Louis, Missouri, United States, 63110
Pfizer Investigational Site Recruiting
St. Louis, Missouri, United States, 63110
United States, New Jersey
Pfizer Investigational Site Recruiting
Hackensack, New Jersey, United States, 07601
Pfizer Investigational Site Recruiting
Teterboro, New Jersey, United States, 07608
United States, New York
Pfizer Investigational Site Recruiting
Buffalo, New York, United States, 14263
United States, Ohio
Pfizer Investigational Site Recruiting
Cleveland, Ohio, United States, 44195
United States, Tennessee
Pfizer Investigational Site Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Pfizer Investigational Site Recruiting
Houston, Texas, United States, 77030
United States, Virginia
Pfizer Investigational Site Recruiting
Richmond, Virginia, United States, 23230
United States, Washington
Pfizer Investigational Site Recruiting
Seattle, Washington, United States, 98195
Pfizer Investigational Site Recruiting
Seattle, Washington, United States, 98109
Canada, Ontario
Pfizer Investigational Site Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Pfizer Investigational Site Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Pfizer Investigational Site Recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
Germany
Pfizer Investigational Site Recruiting
Berlin, Germany, 12203
Pfizer Investigational Site Not yet recruiting
Frankfurt, Germany, 60590
Pfizer Investigational Site Recruiting
Hamburg, Germany, 20246
Pfizer Investigational Site Recruiting
Hannover, Germany, 30625
Pfizer Investigational Site Recruiting
Magdeburg, Germany, 39120
Pfizer Investigational Site Not yet recruiting
Mainz, Germany, 55131
Pfizer Investigational Site Not yet recruiting
Muenster, Germany, 48149
Italy
Pfizer Investigational Site Recruiting
Bologna, Italy, 40138
Pfizer Investigational Site Not yet recruiting
Milano, Italy, 20162
Pfizer Investigational Site Not yet recruiting
Rome, Italy, 00161
Poland
Pfizer Investigational Site Recruiting
Lodz, Lodzkie, Poland, 93-513
Pfizer Investigational Site Not yet recruiting
Warsaw, Mazowieckie, Poland, 02-776
Pfizer Investigational Site Not yet recruiting
Wroclaw, Silesian, Poland, 53-439
Pfizer Investigational Site Recruiting
Gdansk, Poland, 80-952
Pfizer Investigational Site Recruiting
Lodz, Poland, 93-513
Spain
Pfizer Investigational Site Not yet recruiting
Barcelona, Badalona, Spain, 8916
Pfizer Investigational Site Recruiting
Barcelona, Catalunya, Spain, 8035
Pfizer Investigational Site Recruiting
Barcelona, Spain, 08025
Pfizer Investigational Site Not yet recruiting
Barcelona, Spain, 8036
Pfizer Investigational Site Recruiting
Barcelona, Spain, 08003
Pfizer Investigational Site Not yet recruiting
Madrid, Spain, 28033
Pfizer Investigational Site Not yet recruiting
Madrid, Spain, 28034
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: September 9, 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, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease
Pathologic Processes
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
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on September 15, 2014