A Phase I Study of AC220 in Patients With Relapsed/Refractory Acute Myeloid Leukemia Regardless of FLT3 Status
Condition: Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndrome; AML; MDS
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Intervention: AC220
Intervention description: Powder in bottle formulation supplied as 50mg or 350 mg in glass, crimped serum vials. Requires reconstitution by a pharmacist, and must be stored securely and protected from light.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: RTK; kinase; inhibitor; tyrosine; acute; FLT3; AC220; pharmacokinetic; pharmacokinetics; PK; pharmacodynamic; pharmacodynamics; mutations; PD; receptor; class III; relapsed; refractory; t(8;21); q22;q22; AML1/ETO; t(16;16; p13;q22; CBFbeta/MYH11; inv(16); p13q22; 11q23; dysplasia; myeloid; myelomonocytic; monoblastic; monocytic; erythroid; erythroleukemia; megakaryoblastic; basophilic; panmyelosis; myelofibrosis

Summary:

      Patients received oral AC220 daily for 14 days to study the side effects, tolerability and
      best dose for treating relapsed or refractory acute myeloid leukemia, regardless of FLT3
      status.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females age ≥ 18 years;

          2. Histopathologically documented primary or secondary AML, as defined by WHO criteria
             (Jaffe et al, 2001), confirmed by pathology review at treating institution, meeting at
             least one of the following:

               1. Refractory to at least 1 cycle of induction chemotherapy, or

               2. Relapsed after at least 1 cycle of induction chemotherapy, or

               3. Patient is not, according to the clinical judgment of the Principal Investigator,
                  a candidate for induction chemotherapy due to age, comorbidity, or other factors;

          3. Patients for whom no standard therapies are anticipated to result in a durable
             remission, or who have failed potentially curative therapy, or who refuse standard
             therapy or patients for whom there is no known therapy of documented treatment
             benefit;

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;

          5. In the absence of rapidly progressing disease, the interval from prior treatment to
             time of AC220 administration should be at least 2 weeks for cytotoxic agents (other
             than hydroxyurea, per Section 8.8), or at least 5 half-lives for noncytotoxic agents;

          6. Persistent chronic clinically significant toxicities from prior chemotherapy or
             surgery must be less than Grade 2;

          7. Serum creatinine ≤ 2.0 mg/dL;

          8. Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or
             leukemic organ involvement;

          9. Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;

         10. Females of childbearing potential must have a negative pregnancy test (urine β-hCG);

         11. Females of childbearing potential and sexually mature males must agree to use a
             medically accepted method of contraception throughout the study;

         12. Written informed consent must be provided.

        Exclusion Criteria:

          1. Histologic diagnosis of acute promyelocytic leukemia;

          2. Clinically active central nervous system leukemia;

          3. Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or
             higher by the National Cancer Institute Common Terminology Criteria for Adverse Events
             (CTCAE v3);

          4. Bone marrow transplant within 2 months prior to study;

          5. Active, uncontrolled infection;

          6. Major surgery within 4 weeks prior to study;

          7. Radiation therapy within 4 weeks prior to, or concurrent with, study;

          8. Human immunodeficiency virus positivity;

          9. Active hepatitis B or C or other active liver disease;

         10. Women who are pregnant, lactating, or unwilling to use contraception if of
             childbearing potential;

         11. Medical condition, serious intercurrent illness, or other extenuating circumstance
             that, in the judgment of the Principal Investigator, could jeopardize patient safety
             or interfere with the objectives of the study.