Study to Evaluate the Efficacy of Uproleselan in Combination With Chemotherapy in Chinese Patients With R/R AML

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

Detailed Description
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This trial will enroll approximately 140 randomized subjects 18 through 75 years of age at the time of randomization with primary refractory AML or relapsed AML (first or second untreated relapse) and eligible to receive induction chemotherapy as described. Randomization will be done at trial entry at a 1:1 ratio, and will be stratified by age (<60, ≥60 years) and disease status (primary refractory/early relapse ≤6 months, late relapse>6 months) and prior HSCT status. Treatment assignment received at randomization will be maintained during all induction and consolidation cycles. This trial will have the following sequential phases: screening, baseline, induction treatment and count recovery, response assessment, consolidation treatment (if remission is achieved), and follow-up for relapse and survival assessment. Subjects not achieving remission will continue to be followed for long-term trial endpoints such as disease progression and survival. Blinding will be maintained until database lock. All subjects will be followed for long-term outcomes until death or withdrawal of consent.

Official Title
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A Phase 3 Randomized, Double-Blinded Bridging Trial to Evaluate the Efficacy of Uproleselan Administered With Chemotherapy Versus Chemotherapy Alone in Chinese Patients With Relapsed/Refractory Acute Myeloid Leukemia

Conditions
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Relapsed/Refractory AML

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 AML diagnosed with ≥20% myeloid marrow blasts or peripheral blood blasts per WHO criteria(2008) at the time of initial diagnosis For refractory AML, only cytarabine/daunorubicin(or Idarubicin) as can be applied repeatedly(maximal twice) as induction, no other chemotherapy are allowed to be applied Venatoclax /hypomethylation drug [HMA] can be used before and after chemotherapy. For relapse AML, it must be the first or second relapse, and remain untreated. Certain regimens (Venatoclax/HMA, Venetoclax/LDAC, HMA single agent) and FLT3 inhibitors, tyrosine kinase inhibitors, IDH1/IDH2 inhibitors or similar targeted inhibitors used alone are not considered cytotoxic chemotherapy are allowed. 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 Active signs or symptoms of CNS involvement by malignancy (No lumbar puncture required) Prior use of G-CSF, CM-CSF or plerixafor within 7 days of dosing. 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 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
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

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. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate(rate of CR, CR/CRi and CR/CRh) | Defined as the rate of subjects who reach CR, CR/CRi and CR/CRh | Up to 60 days | 
| Duration of remission | Time from date of first documented remission to date of relapse or death from any cause, whichever occurs first. | Up to 3 years | 
| Event-free survival | Time from date of randomization into the study to the date of treatment failure, relapse, or death from any cause; whichever occurs first. | Up to 3 years | 
| Rate of severe oral mucositis | Incidence of severe oral mucositis experienced in patients after treatment. | Up to 254 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML