Hedgehog Inhibitor PF-04449913 in Treating Patients with Acute Myeloid Leukemia at High Risk of Relapse after Donor Stem Cell Transplant

Status: Closed to Accrual


This phase II trial studies how well Hedgehog inhibitor PF-04449913 works in treating patients with acute myeloid leukemia at high risk of relapse after donor stem cell transplant. Drugs used in chemotherapy, such as Hedgehog inhibitor PF-04449913, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Eligibility Criteria

Inclusion Criteria

  • World Health Organization (WHO)-confirmed acute myeloid leukemia (AML)
  • Between days 28 and 50 post transplantation at the time of initiation of the study drug
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy > 2 months
  • Recipient of a myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant (HSCT): * Conditioning regimen to be prescribed at investigator’s discretion, but will be prospectively defined as myeloablative or non-myeloablative
  • Stable engraftment, as defined by absolute neutrophil count (ANC) >= 1000/mm^3 and platelets >= 25,000/mm^3
  • In morphologic remission (< 5% marrow blasts) based on bone marrow (BM) biopsy performed +/- 5 days of day 28 post-transplantation
  • Without clinical signs of active central nervous system disease
  • For non-myeloablative transplants, >= 50% cluster of differentiation (CD)3 donor chimerism at screening
  • High risk of relapse after HSCT, defined as the presence of minimal residual disease as measured by flow cytometry in the absence of evidence of morphologic disease on a bone marrow biopsy prior to HSCT
  • Aspartate aminotransferase (AST), alanine aminotransferase, (ALT) =< 3.0 x institutional upper limit of normal (ULN)
  • Total bilirubin =< 2.0 x institutional ULN, unless documented Gilbert’s syndrome
  • Either creatinine < 1.5 x institutional upper limit of normal (ULN) or creatinine clearance > 60 mL/min as calculated by institution’s standard formula
  • Serum/urine pregnancy test (for females of childbearing potential) that is negative within 72 hours prior to initiation of first dose of treatment (a patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active)
  • Female patients of childbearing potential and sexually active males and female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 90 days after the last dose of assigned treatment
  • Subject is able to comply with study procedures and follow-up examinations

Exclusion Criteria

  • Concomitant treatment with other anti-neoplastic agents, with the exception, when clinically indicated, of prophylaxis in the post-transplantation setting with intrathecal chemotherapy
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Inability to swallow or absorb drug
  • Active uncontrolled acute fungal, bacterial, or other infection that is unresponsive to therapy at time of study drug dosing
  • Unstable angina pectoris
  • New York Heart Association class III or IV heart failure
  • Corrected QT (QTc) interval (using Fridericia’s correction formula, QTcF, if prolonged) > 470 msec
  • Active cardiac arrhythmias with rapid ventricular response (defined as heart rate greater than 100 beats/minute)
  • Known human immunodeficiency virus (HIV) infection
  • Grade III/IV acute graft-versus-host disease (GVHD)
  • Current use or anticipated need for food or drugs that are known moderate/strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers, with the exception of azole antifungals, which are permitted
  • Any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures
  • Pregnant or lactating females

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline


I. Determine whether PF-04449913 (Hedgehog inhibitor PF-04449913) can prevent relapse in high risk acute myeloid leukemia patients who receive an allogeneic stem cell transplantation.


I. Determine the toxicity profile of PF-04449913 in this population.

II. Determine the impact of this intervention on overall survival (OS).


Beginning 28-50 days after allogeneic stem cell transplant, patients receive Hedgehog inhibitor PF-04449913 orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then annually for 5 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
University of Colorado Hospital

Principal Investigator
Daniel A. Pollyea

Trial IDs

Primary ID 12-1558
Secondary IDs NCI-2013-00824, 12-1558.cc
Clinicaltrials.gov ID NCT01841333