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

GlycoMimetics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: GMI-1271; Drug: Idarubicin; Drug: Etoposide; Drug: Cytarabine; Drug: Mitoxantrone

Study type: Interventional

Funder types: Industry

Identifiers

NCT02306291

GMI-1271-201

Details and patient eligibility

About

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.

Enrollment: 91 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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91 participants in 3 patient groups

Arm A (Phase I)

Experimental group

Description:

GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older

Treatment:

Drug: Cytarabine

Drug: Etoposide

Drug: GMI-1271

Drug: Mitoxantrone

Arm B (Phase II Arm A)

Experimental group

Description:

GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older

Treatment:

Drug: Cytarabine

Drug: Etoposide

Drug: GMI-1271

Drug: Mitoxantrone

Arm C (Phase II Arm B)

Experimental group

Description:

GMI-1271 in combination with cytarabine and idarubicin (7+3 regimen) in newly diagnosed subjects 60 years and older

Treatment:

Drug: Cytarabine

Drug: Idarubicin

Drug: GMI-1271