Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Properties of Oral AT-406 in Combination With Daunorubicin and Cytarabine in Patients With Poor-risk Acute Myelogenous Leukemia (AML)

Study Overview
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Brief Summary
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The main purpose of this study are to determine the maximum dose of AT-406 that can be safely given in combination with cytarabine and daunorubicin to humans. Other purposes are to determine how the drug is broken down in the body, and to see if there are any molecular interactions that can help determine how AT-406 works. Side effects will also be studied in an effort to make sure that this drug is safe to take.

Detailed Description
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This is an open label, multi-center, dose escalation study to determine the MTD of oral AT-406 combined with daunorubicin and cytarabine in patients with poor-risk AML. Treatment with AT-406 will be administered to up to 60 patients at approximately 7 investigational sites in the US. Patients will be enrolled in open label sequential cohorts of up to 12 patients to determine the MTD of AT-406 in combination with daunorubicin and cytarabine. Dose finding will occur during the induction cycle of the regimen. AT-406 will not be administered in consolidation cycles. Patients who require re-induction during initial treatment will be removed from the study and replaced (if needed) in order to assess at least 3 evaluable patients at each dose level. Clinical and laboratory parameters will be assessed to evaluate the toxicity of AT-406. In addition, pharmacokinetic (PK) and pharmacodynamic (PDy) blood samples will be analyzed for plasma concentrations and PDy effect of AT-406, respectively.

Official Title
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Phase I Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Properties of Oral AT-406 in Combination With Daunorubicin and Cytarabine in Patients With Poor-risk, Acute Myelogenous Leukemia (AML)

Conditions
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Acute Myelogenous Leukemia (AML)

Intervention / Treatment
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* Drug: AT-406 in combination with daunorubicin and cytarabine


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: Inclusion: Male or females patients ages 18 to 74 Morphological diagnosis of untreated or relapsed non-M3 AML according to WHO diagnostic criteria who exhibit at least one poor-risk feature and are not be known to exhibit any favorable cytogenetic features or variants. Patients with relapsed AML and patients with prior autologous or allogeneic hematopoietic stem cell transplantations are eligible if relapse occurred following a remission of ≥ 6 months. Patients must have an ECOG score of ≤ 2, Adequate cardiac, liver and renal function. Exclusion: Must not have any evidence of CNS leukemia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: AT-406 in combination with daunorubicin and cytarabine|Oral AT-406 (capsule) given once daily on days 1-5 of induction therapy with daunorubicin 90 mg/m2 I.v. on days 1-3 and cytarabine 100 mg/m2 i.v. by continuous infusion on days 107 of induction therapy.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Number of Participants with Adverse Events as a Measure of Safety and Tolerability of oral AT-406 in combination with daunorubicin and cytarabine. | Determine Number of Participants with Adverse Events as a Measure of Safety and Tolerability of AT-101. | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the pharmacokinetic profile of AT-406 and daunorubicin and cytarabine | To determine how the drug is absorbed, distributed, metabolized, and eliminated by the body. | 15 months | 

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