Study to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in AML

A Phase I/II, Open-label Multicenter Trial to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia

This study will evaluate GMI-1271, a specific E-selectin antagonist, in acute myeloid leukemia in combination with standard agents used to treat this disease.

Inclusion criteria:

1. AML (including secondary AML) diagnosed as per WHO criteria

2. For relapsed/refractory subjects only:

   • Subjects age ≥ 18 years with relapsed or refractory AML after ≤ 2 prior induction regimens, at least one containing anthracyclines
   • Medically eligible to receive MEC
   • Absolute blast count (ABC) ≤ 40,000/mm

3. For treatment-naïve subjects only:

   • Subjects ≥ 60 years of age with newly diagnosed AML
   • Medically eligible to receive "7+3" cytarabine/idarubicin
   • ABC count ≤ 40,000/mm

4. ECOG performance status 0-2

5. Hemodynamically stable and adequate organ function

Exclusion criteria:

1. Acute promyelocytic leukemia
2. Acute leukemia of ambiguous lineage (biphenotypic leukemia)
3. Active signs or symptoms of CNS involvement by malignancy
4. No prior G-CSF, GM-CSF or plerixafor within 14 days of study drug dosing
5. Known history or evidence of active hepatitis A, B, or C or HIV
6. Uncontrolled acute life threatening bacterial, viral or fungal infection
7. Active graft versus host disease (GVHD) ≥ Grade 2 or extensive chronic GVHD requiring immunosuppressive therapy
8. Hematopoietic stem cell transplantation ≤ 4 months of dosing
9. Clinically significant cardiovascular disease