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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: GMI-1271
* Drug: Mitoxantrone
* Drug: Etoposide
* Drug: Cytarabine
* Drug: Idarubicin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: AML (including secondary AML) diagnosed as per WHO criteria 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 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 ECOG performance status 0-2 Hemodynamically stable and adequate organ function Exclusion criteria: Acute promyelocytic leukemia Acute leukemia of ambiguous lineage (biphenotypic leukemia) Active signs or symptoms of CNS involvement by malignancy No prior G-CSF, GM-CSF or plerixafor within 14 days of study drug dosing Known history or evidence of active hepatitis A, B, or C or HIV Uncontrolled acute life threatening bacterial, viral or fungal infection Active graft versus host disease (GVHD) ≥ Grade 2 or extensive chronic GVHD requiring immunosuppressive therapy Hematopoietic stem cell transplantation ≤ 4 months of dosing Clinically significant cardiovascular disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Phase I)<br>GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older | Drug: GMI-1271<br>* E-selectin antagonist<br>* Other names: Uproleselan;Drug: Mitoxantrone<br>* induction chemotherapy<br>Drug: Etoposide<br>* induction chemotherapy<br>Drug: Cytarabine<br>* induction chemotherapy<br>|
| Experimental: Arm B (Phase II Arm A)<br>GMI-1271 in combination with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory subjects 18 years and older | Drug: GMI-1271<br>* E-selectin antagonist<br>* Other names: Uproleselan;Drug: Mitoxantrone<br>* induction chemotherapy<br>Drug: Etoposide<br>* induction chemotherapy<br>Drug: Cytarabine<br>* induction chemotherapy<br>|
| Experimental: Arm C (Phase II Arm B)<br>GMI-1271 in combination with cytarabine and idarubicin (7+3 regimen) in newly diagnosed subjects 60 years and older | Drug: GMI-1271<br>* E-selectin antagonist<br>* Other names: Uproleselan;Drug: Cytarabine<br>* induction chemotherapy<br>Drug: Idarubicin<br>* induction chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by frequency, severity and relatedness of adverse events |  | up to 44 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time versus plasma concentration profile of GMI-1271 | Plasma concentration of GMI-1271 | up to 11 days | 
| Overall response rate | Proportion of subjects who achieve a complete response (CR) or CR with incomplete blood count recovery (CRi) per local investigator assessment | up to 12 months | 
| Time to response | Time from date of first dose to first documentation of response | up to 12 months | 
| Duration of response | Time from date of first documented remission to the date of relapse or death from any cause, whichever occurs first | up to 12 months | 
| Event-free survival | Time from date of first dose to the date of treatment failure, relapse, or death from any cause, whichever occurs first | up to 12 months | 
| Overall survival | The probability of survival at 6 months (Phase 1) and 12 months (Phase 2), after the date of first dose of study drug | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, Acute myeloid leukemia, E-selectin, relapse refractory, elderly newly diagnosed, induction