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

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).

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: ARRY-614, p38/Tie2 inhibitor; oral

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University, Winship Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Array Biopharma, now a wholly owned subsidiary of Pfizer

Publications and helpful links

General Publications

• Su H, Jiang M, Senevirathne C, Aluri S, Zhang T, Guo H, Xavier-Ferrucio J, Jin S, Tran NT, Liu SM, Sun CW, Zhu Y, Zhao Q, Chen Y, Cable L, Shen Y, Liu J, Qu CK, Han X, Klug CA, Bhatia R, Chen Y, Nimer SD, Zheng YG, Iancu-Rubin C, Jin J, Deng H, Krause DS, Xiang J, Verma A, Luo M, Zhao X. Methylation of dual-specificity phosphatase 4 controls cell differentiation. Cell Rep. 2021 Jul 27;36(4):109421. doi: 10.1016/j.celrep.2021.109421.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): March 18, 2015

Study Registration Dates

• First Submitted: November 28, 2011
• First Submitted That Met QC Criteria: December 20, 2011
• First Posted (Estimate): December 21, 2011

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: ARRAY-614-112