A Study of ARRY-520 in Patients With Advanced Myeloid Leukemia

Study Overview
=================
Brief Summary
-----------------
This is a 2-phase study during which patients with select myeloid leukemias or advanced myelodysplastic syndrome (MDS), who have failed, refused or are not eligible for standard treatment, will receive investigational study drug ARRY-520. The study has 3 parts. The first phase of the study, Phase 1, has 2 parts. In the first part of Phase 1, patients with select myeloid leukemias or advanced MDS will receive increasing doses of study drug on different schedules in order to achieve the highest dose possible that will not cause unacceptable side effects. Approximately 30 patients (per schedule) from the US will be enrolled in Part 1 (Completed). In the second part of Phase 1, patients with advanced MDS will receive the best dose of study drug and schedule determined from the first part of the study. Approximately 10 patients from the US will be enrolled in Part 2 (Completed). In the third part of the study, Phase 2, patients with acute myeloid leukemia (AML) or advanced MDS will receive the best dose of study drug and schedule determined from the first part of the study and will be followed to see what side effects the study drug causes and to see what effectiveness it has, if any, in treating the cancer. Approximately 40 patients from the US will be enrolled in Part 3 (Withdrawn).

Official Title
-----------------
A Phase 1/2 Study of ARRY-520 in Patients With Advanced Myeloid Leukemia

Conditions
-----------------
Advanced MDS, Acute Myeloid Leukemia

Intervention / Treatment
-----------------
* Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria (Part 2): Patients with either Intermediate-2 or High risk MDS or with AML (>20% bone marrow blasts) with stable low or normal white blood cell count (WBC). Patients should have failed one prior chemotherapy regimen which should have included a hypomethylating agent. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2. Discontinuation of prior treatment at least 2 weeks prior to the start of the study. Adequate hepatic and renal function. Additional criteria exist. Key Exclusion Criteria (Part 2): Concurrent cytotoxic therapy, or biological, endocrine and immunological response modifiers. Previous radiation to >25% of bone marrow. Other active malignancies. Known positive serology for the human immunodeficiency virus (HIV). Central nervous system involvement as documented by spinal fluid cytology. Active, uncontrolled infection. Additional criteria exist

Ages Eligible for Study
-----------------
Minimum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARRY-520<br> | Drug: ARRY-520, KSP(Eg5) inhibitor; intravenous<br>* Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule; Part 3: multiple dose, single schedule.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish the maximum tolerated dose (MTD) of the study drug. |  | Part 1 | 
| Characterize the pharmacokinetics (PK) of the study drug. |  | Part 1 | 
| Characterize the safety profile of the study drug in terms of adverse events, dose limiting toxicity, clinical laboratory tests, weight, electrocardiograms and physical examinations. |  | Part 1 and Part 2 | 
| Assess the efficacy of the study drug in terms of incidence of complete remission (CR) and hematologic improvement (CRp). |  | Part 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of the study drug in terms of incidence of CR and CRp. |  | Part 1 and Part 2 | 
| Characterize the safety profile of the study drug in terms of adverse events, dose limiting toxicity, clinical laboratory tests, weight, electrocardiograms and physical examinations. |  | Part 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
preleukemia, dysplasia of myeloid blood cells