PF-04449913 For Patients With Acute Myeloid Leukemia at High Risk of Relapse After Donor Stem Cell Transplant
Condition: Adult Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: PF-04449913
Intervention description: 100mg given orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloid leukemia in remission; Recurrent myeloid leukemia

Summary:

      This phase II trial will test whether the Hedgehog signaling pathway inhibitor PF-04449913
      can decrease disease relapse in high-risk patients with acute myeloid leukemia after donor
      stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  WHO-confirmed AML

          -  Age ≥18 years

          -  Between days 28 and 50 post transplantation at the time of initiation of the study
             drug

          -  ECOG performance status ≤ 2 (See Appendix A: ECOG Performance Status Scale)

          -  Life expectancy > 2 months

          -  Recipient of a myeloablative or non-myeloablative allogeneic 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/mm3 and
             platelets ≥ 25,000/mm3

          -  In morphologic remission (< 5% marrow blasts) based on BM biopsy performed +/- 5 days
             of day 28 post- transplantation

          -  Without clinical signs of active central nervous system disease

          -  For non-myeloablative transplants, ≥50% CD3 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

          -  Adequate organ function as indicated by the following laboratory values:

               -  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

          -  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 HIV infection

          -  Grade III/IV acute GVHD

          -  Current use or anticipated need for food or drugs that are known moderate/strong
             CYP3A4 inducers (See Table 1 and section 5.9.2: Prohibited Concomitant Therapy), 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