Phase I/II, Open-label, Multi-center, Two Part Dose-escalation, Safety, Pharmacokinetics (PK) and Efficacy Study of AZD4877 in Patients With Acute Myelogenous Leukemia (AML)

Study Overview
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Brief Summary
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The primary purpose of this study is to find out what the maximum tolerated dose is for an experimental drug called AZD4877 based on the side effects experienced by patients that receive AZD4877 on a daily times 3 schedule in acute myelogenous leukemia (AML). For enrollment information see the Central Contact information below

Official Title
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A Phase I/II, Open-Label, Multi-Center, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of AZD4877 Administered on Days 1, 2 and 3 in Adult Patients With Recurrent or Refractory Acute Myelogenous Leukemia (AML) Excluding Promyelocytic Leukemia

Conditions
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Acute Myelogenous Leukemia

Intervention / Treatment
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* Drug: AZD4877


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A: Relapsed or refractory leukemia for which no standard therapies are anticipated to result in a durable remission Part B: AML who have had no more than two prior relapses or failed to achieve remission after at least one induction treatment. Patients with prior allogeneic transplants who remain clinically stable for ≥2 weeks or more off immunosuppressive therapy Exclusion Criteria: Promyelocytic acute myelogenous leukemia Prior allogeneic transplant requiring immunosuppressive therapy or treating physician does not consider patient to be a candidate for allogeneic transplantation. Liver injury

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: AZD4877|intravenous infusion administered on days 1, 2 and 3|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs) | To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs) | Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period. | 
| To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR) | Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure. | Response is evaluated after a maximum of 2 courses of induction therapy. | 
| To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ] | Maximum plasma concentration, Cmax | PK samples are collected on Days 1, 2, 3, 24 and 48 hours following the end of Day 3 AZD4877 infusion and Day 8. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Effect of AZD4877 on Rate and Duration of CR, CRi, PR and Overall Response (CR,CRi, or PR) | Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure. | Response is evaluated after a maximum of 2 courses of induction therapy. | 
| To Evaluate the Safety and Tolerability of AZD4877 on a Daily x 3 Schedule by Assessment of Adverse Events, Non-hematologic Labs and Vital Signs |  | Patients were followed for safety from the date of first dose of AZD4877 up to 30-days after the last administration of AZD4877, where possible. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Phase II, acute myelogenous leukemia, AML, cancer