A Study of ARRY-614 in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes

Study Overview
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Brief Summary
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This is a Phase 1 study during which patients with low or intermediate-1 risk myelodysplastic syndromes (MDS) will receive investigational study drug ARRY-614. This study has 2 parts. In the first part, patients will receive increasing doses of study drug in order to achieve the highest dose of the study drug possible that will not cause unacceptable side effects. Approximately 50 patients from the US will be enrolled in Part 1 (Completed). In the second part of the study, patients will receive the best dose of study drug determined from the first part of the study and will be followed to see what side effects and effectiveness the study drug has, if any, in treating the cancer. Approximately 30 patients from the US will be enrolled in Part 2 (Completed).

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: ARRY-614, p38/Tie2 inhibitor; oral


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria (Part 1 and Part 2): Diagnosis of MDS by bone marrow biopsy. International Prognostic Scoring System (IPSS) score of low or intermediate-1 risk MDS. May have received prior therapy for MDS. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2. Adequate liver and renal function. Additional criteria exist. Key Exclusion Criteria (Part 1 and Part 2): History of bone marrow transplant. Treatment for MDS other than transfusions or a stable dose (≥ 4 weeks) of hematopoietic growth factors on the day of the first dose of study drug. Concomitant malignancies or previous malignancies with less than a 2-year disease-free interval at the time of enrollment. Treatment with an investigational medicinal product that is not expected to be cleared by the first dose of study drug or that has demonstrated to have prolonged side effects. Treatment with azacitidine or decitabine within 2 weeks prior to first dose of study drug. Chronic use (> 2 weeks) of greater than physiologic doses of corticosteroids (dose equivalent to > 20 mg/day of prednisone) within 4 weeks prior to first dose of study drug. Treatment with an immunomodulatory agent within 4 weeks prior to the first dose of study drug. Additional criteria exist.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARRY-614<br> | Drug: ARRY-614, p38/Tie2 inhibitor; oral<br>* Part 1: multiple dose, escalating; Part 2: multiple dose, single schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish the maximum tolerated dose (MTD) of study drug. |  | Part 1, 9 months | 
| Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms. |  | Part 1, 9 months; Part 2, 9 months | 
| Characterize the pharmacokinetics (PK) of the study drug and a metabolite in terms of plasma concentrations. |  | Part 1, 9 months; Part 2, 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of the study drug in terms of response, time to response, duration of response, overall survival, hematologic improvement and platelet transfusion independence/reduction. |  | Part 1, 9 months; Part 2, 9 months |