An Open Label, Single Centre Mass Balance C14 Study in Patients With Acute Myeloid Leukaemia (AML)

Study Overview
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Brief Summary
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The purpose of the study is to assess how AZD1152 is absorbed or excreted in and out of the body in patients with Acute Myeloid Leukaemia (AML).

Official Title
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A Phase I Open, Non-randomised, Single-centre Study to Assess the Metabolism, Excretion and Pharmacokinetics of AZD1152 and AZD1152 hQPA Following Intravenous Administration of [14C]-AZD1152 in Patients With Acute Myeloid Leukaemia (AML)

Conditions
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Acute Myeloid Leukaemia

Intervention / Treatment
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* Drug: AZD1152
* Drug: C14 AZD1152


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsed or refractory AML for which no standard therapies are anticipated to result in durable remission. Or, patients with newly diagnosed AML who are not considered to be suitable for standard induction and consolidation chemotherapy Ability to stay in hospital for up to 9 days on the [14C] AZD1152 treatment cycle. Subjects who have relapsed > 1 year following myeloablative therapy with allogeneic bone marrow or stem cell transplantation may be eligible if they have no or limited evidence of extensive graft-versus-host disease Exclusion Criteria: QTc interval ≥470 ms calculated from a single ECG reading or a mean of 3 ECG readings using Fridericia's or Bazett's correction Administration of hydroxyurea to control peripheral blood counts is prohibited within 24 hours prior to first dose of study drug Any chemotherapy or radiotherapy within 14 days prior to starting the study (not including palliative radiotherapy at focal sites)

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD1152<br>100 mg Lyophile 5 mL Diluent | Drug: AZD1152<br>* 100mg Lyophile, 5mL Diluent IV infusion<br>|
| Experimental: C14 AZD1152<br>AZD1152 radiolabelled IV solution. 1.05 mg/ml will be presented as a 15 ml fill in a 20 ml vial. | Drug: C14 AZD1152<br>* radiolabelled IV solution, 1.05 mg/ml presented as 15 ml fill in 20ml vial infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The concentration of total radioactivity, AZD1152 and AZD1152 hQPA in plasma and their ratios, the concentration of total radioactivity in blood and its blood/plasma concentration ratios |  | Day1-10 | 
| The derived plasma and urinary pharmacokinetic parameters for AZD1152 and AZD1152 hQPA The percentage of the [14C] AZD1152 dose recovered in urine, faeces and vomit (if presented), and the percentage of radioactive dose recovered overall. |  | Day1-10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs), serious adverse events (SAEs) and deaths, Discontinuations for tolerability reasons, vital signs (temperature, blood pressure [BP], pulse rate and respiratory rate [RR]) |  | AEs, SAEs, deaths, discontinuations ongoing to completion and vitals over 22 days - Screening, PD Day 1, Days 3, 6, 9, 14, 22 | 
| Electrocardiogram (ECG) parameters |  | Screening, PD Day 1, Day 4 | 
| Clinical chemistry, haematology (including clotting parameters) and urinalysis; physical examination |  | Chemistry/Heamatology - Screening, PD Day 1, Days 3, 6, 9, 14, 22Urinalysis - Screening, PD Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, Acute Myeloid Leukaemia (AML), AZD1152, Pharmacokinetics