Study to Determine the Efficacy of Uproleselan (GMI-1271) in Combination With Chemotherapy to Treat Relapsed/Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This study will evaluate the efficacy of uproleselan (GMI-1271), a specific E-selectin antagonist, in combination with chemotherapy to treat relapsed/refractory AML, compared to chemotherapy alone. The safety of uproleselan when given with chemotherapy will also be investigated in patients with relapsed/refractory AML

Official Title
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A Phase III Randomized, Double-Blind Trial to Evaluate the Efficacy of Uproleselan Administered With Chemotherapy Versus Chemotherapy Alone in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Uproleselan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years and ≤75 years in age Patients with relapsed or refractory AML No more than one prior stem cell transplant Has not received the chemotherapy regimen to be used for induction on this trial Is considered medically eligible to receive the chemotherapy regimen to be used for induction on this trial Exclusion Criteria: Patients with acute promyelocytic leukemia, acute leukemia of ambiguous lineage (biphenotypic leukemia), chronic myeloid leukemia with myeloid blast crisis, or secondary refractory AML. Active signs or symptoms of CNS involvement by malignancy. Stem cell transplantation ≤4 months prior to dosing. Any immunotherapy or radiotherapy therapy within 28 days of dosing; any other experimental therapy or chemotherapy within 14 days of dosing. Prior use of G-CSF, CM-CSF or plerixafor within 7 days of dosing. Inadequate organ function. Abnormal liver function. Known active infection with hepatitis A, B, or C, or human immunodeficiency virus. Moderate kidney dysfunction (glomerular filtration rate <45 mL/min). Uncontrolled acute life-threatening bacterial, viral, or fungal infection. Clinically significant cardiovascular disease. Major surgery within 4 weeks of dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Uproleselan (GMI-1271)<br>Uproleselan in combination with mitoxantrone, etoposide and cytarabine (MEC) or fludarabine, cytarabine and idarubicin (FAI) | Drug: Uproleselan<br>* A rationally designed E-selectin antagonist used to inhibit binding of cells to E-selectin<br>|
| Placebo Comparator: Placebo (Saline, 0.9% Sodium Chloride)<br>Placebo in combination with mitoxantrone, etoposide and cytarabine (MEC) or fludarabine, cytarabine and idarubicin (FAI) | Drug: Placebo<br>* Saline, 0.9% Sodium Chloride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from the date of randomization into the study to the date of death. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of severe oral mucositis | Incidence of severe oral mucositis experienced in patients after treatment. | up to 60 days | 
| Overall response rate | Proportion of subjects who achieve a complete remission [CR] or CR with partial recovery [CRh] of blood counts | Up to 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, Refractory AML, acute myeloid leukemia, Relapsed AML