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 May 2015 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01546038
First received: March 1, 2012
Last updated: May 1, 2015
Last verified: May 2015
  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 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: 254
Study Start Date: June 2012
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: March 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
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35249-6909
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
University of Alabama at Birmingham - Drug Shipment Recruiting
Birmingham, Alabama, United States, 35249
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
United States, California
Genoptix Medical Laboratory Recruiting
Carlsbad, California, United States, 92008
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
USC/Norris Comprehensive Cancer Center / Investigational Drug Services Recruiting
Los Angeles, California, United States, 90033
Keck Hospital of USC Recruiting
Los Angeles, California, United States, 90033
Ronald Reagan UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Ronald Reagan UCLA Medical Center Drug Information Center (INVESTIGATION DRUG SHIPMENT) Recruiting
Los Angeles, California, United States, 90095
UCLA Recruiting
Los Angeles, California, United States, 90095
UCLA Drug lnformation/lnvestigational Drugs Recruiting
Los Angeles, California, United States, 90095
USC/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
LAC & USC Medical Center Recruiting
Los Angeles, California, United States, 90033
United States, Colorado
Anschutz Cancer Pavilion Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute, Inc. Recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Investigational Drug Service, Emory University Clinic Recruiting
Atlanta, Georgia, United States, 30322
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Northwestern Medicine Developmental Therapeutics Institute Recruiting
Chicago, Illinois, United States, 60611
Northwestern Medical Faculty Foundation Recruiting
Chicago, Illinois, United States, 60611
Northwestern Memorial Hospital: DRUG SHIPMENT ADDRESS Recruiting
Chicago, Illinois, United States, 60611
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
The University of Chicago Recruiting
Chicago, Illinois, United States, 60637
The University of Chicago (2) Recruiting
Chicago, Illinois, United States, 60637
United States, Indiana
Covance Central Lab Recruiting
Indianapolis, Indiana, United States, 46214
United States, Kansas
University of Kansas Clinical Research Center Recruiting
Fairway, Kansas, United States, 66205
University of Kansas Hospital Recruiting
Kansas City, Kansas, United States, 66160
University of Kansas Cancer Center and Medical Pavilion Recruiting
Westwood, Kansas, United States, 66205
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute (DFCI) Recruiting
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
University of Michigan Comprehensive Cancer Center Clinical Trials Office - Administrative Only Recruiting
Ann Arbor, Michigan, United States, 48109-2800
United States, Missouri
Siteman Cancer Center - West County Recruiting
Creve Coeur, Missouri, United States, 63141
Washington University School of Medicine - Siteman Cancer Center Recruiting
St. Louis, Missouri, United States, 63110
Barnes-Jewish Hospital Recruiting
St. Louis, Missouri, United States, 63110
PI: Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Barnes Jewish Hospital North Campus Recruiting
St. Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
John Theurer Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
John Theurer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
United States, Tennessee
Centennial Medical Center Recruiting
Nashville, Tennessee, United States, 37203
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Virginia
PPD Recruiting
Richmond, Virginia, United States, 23230
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
University of Washington- Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Canada, Ontario
Juravisnki Cancer Centre @ Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Princess Margaret Cancer Centre Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Centre de Sante et de Services Sociaux (CSSS) Champlain - Charles-Le Moyne Recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
Germany
Universitaetsklinikum Ulm Not yet recruiting
Ulm, Baden-Wuerttemberg, Germany, 89081
Charite-Universitatsmedizin Berlin, Med. Kl. m. S. Hamatologie, Onkologie und Tumorimmunologie, Recruiting
Berlin, Germany, 13353
Med. Klinik fuer Haematologie, Onkologie - Charite Campus Rudolf-Virchow-Klinikum Recruiting
Berlin, Germany, 12200
Johann Wolfgang Goethe University, Dept. of Medicine, Hematology and Oncology Recruiting
Frankfurt, Germany, 60590
Universitatsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Staedtisches Krankenhaus Kiel gGmbH Recruiting
Kiel, Germany, 24116
Universitatsklinikum Magdeburg A.o.R. Recruiting
Magdeburg, Germany, 39120
Centrum fuer Thrombose und Haemostase -Johannes Gutenberg-Universitaet Mainz Recruiting
Mainz, Germany, 55131
Johannes Gutenberg-Universitaet Mainz Recruiting
Mainz, Germany, 55131
Universitaetsklinikum Muenster Recruiting
Muenster, Germany, 48149
Italy
Policlinico S. Orsola-Malpighi di Bologna Recruiting
Bologna, Italy, 40138
A.O. Ospedale Niguarda Ca Granda - SC Ematologia Not yet recruiting
Milano, Italy, 20162
Policlinico Universitario "Umberto I" Universita degli Studi "La Sapienza" Sezione di Ematologia Recruiting
Rome, Italy, 00161
A.O. Citta della Salute e della Scienza di Torino - S.C. Ematologia Recruiting
Torino, Italy, 10126
A.O.U. Santa Maria della Misericordia Recruiting
Udine, Italy, 33100
Poland
Oddzial Hematologii Recruiting
Lodz, Lodzkie, Poland, 93-513
Instytut Hematologii i Transfuzjologii (IHT) (Institute of Haematology and Transfusion Medicine) Not yet recruiting
Warsaw, Mazowieckie, Poland, 02-776
Dolnoslakie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku Recruiting
Wroclaw, Silesian, Poland, 53-439
Akademickie Centrum Kliniczne - Szpital Akademii Medycznej W Gdansku Recruiting
Gdansk, Poland, 80-952
Oddzial hematologii-Klinika Hematologii wojewódzki szpital Specjalistyczny im. M. Kopernika w Lodzi Recruiting
Lodz, Poland, 93-513
Spain
Hospital Virgen Del Rocio Not yet recruiting
Sevilla, Andalucia, Spain, 41013
Institut Catala d'Oncologia, Hospital Universitari Germans Trias I Pujol Recruiting
Barcelona, Badalona, Spain, 08916
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Catalunya, Spain, 08035
Hospital del Mar Recruiting
Barcelona, Spain, 08003
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Park de Salut Mar - Hospital del Mar Recruiting
Barcelona, Spain, 08003
Hematology Dpt., Hospital Clinic of Barcelona Recruiting
Barcelona, Spain, 8036
Hospital Universitario Reina Sofia Not yet recruiting
Cordoba, Spain, 14004
Hospital Ramon y Cajal Recruiting
Madrid, Spain, 28034
MD Anderson Cancer Center Not yet recruiting
Madrid, Spain, 28033
Hospital Universitario y Politecnico La Fe Not yet recruiting
Valencia, Spain, 46026
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, 2012-000684-24
Study First Received: March 1, 2012
Last Updated: May 1, 2015
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
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions
Cytarabine
Daunorubicin
Decitabine
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on May 25, 2015