Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)
Status: | Recruiting |
---|---|
Conditions: | Blood Cancer, Hematology |
Therapuetic Areas: | Hematology, Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 10/19/2013 |
Start Date: | June 2012 |
End Date: | June 2021 |
Contact: | Nikolaus S. Trede, MD, PhD |
Email: | nikolaus.trede@ariad.com |
Phone: | (617) 494-0400 |
A Phase 3 Randomized,Open-Label Study of Ponatinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase
The purpose of this study is to compare the efficacy of ponatinib and imatinib in patients
with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase.
This multicenter, international, phase 3 trial will test the hypothesis that ponatinib is an
effective treatment for newly diagnosed CP-CML patients when compared with standard
imatinib.
Patients will be randomized in a 1:1 fashion, stratified by Sokal risk score at diagnosis
(low, intermediate, high), to receive once daily oral administration of either ponatinib or
imatinib. Efficacy measures include molecular, cytogenetic, and hematologic response rates
at various timepoints; time to, duration of, and durability of responses; and survival
follow-up. Safety measures include clinical laboratory testing, adverse event monitoring,
vital signs, physical exams, ECGs, and ECHOs. Other measures include two patient-reported
health outcomes questionnaires (FACT-Leu and EQ-5D-5L), determination of mutation status,
and, for ponatinib only, measurement of steady-state plasma concentration. Accrual is
expected to take approximately 2 years, and patients will be followed for survival for up to
8 years after the last patient's first dose; therefore, patient participation may last up to
10 years.
Inclusion Criteria:
1. CP CML within 6 months of diagnosis
- CP-CML will be defined by (i) <15% blasts in bone marrow; (ii) <30% blasts plus
promyelocytes in bone marrow; (iii) <20% basophils in peripheral blood; (iv)
≥100 × 10^9/L platelets (≥100,000/mm^3); (v) No evidence of extramedullary
disease except hepatosplenomegaly; AND (vi) No prior diagnosis of AP-CML or
BP-CML
2. Cytogenetic assessment must demonstrate the BCR-ABL fusion by presence of the t(9;22)
Philadelphia chromosome
- (a)Variant translocations are only allowed provided they are assessable for
cytogenetic response utilizing conventional cytogenetic techniques; (b)
Conventional chromosome banding must be performed; AND (c) A minimum of 20
metaphases must be assessable at entry
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
4. Adequate hepatic function as defined by the following criteria:
(a) Total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's
syndrome; (b) Alanine aminotransferase (ALT) ≤2.5 × ULN; AND (c) Aspartate
aminotransferase (AST) ≤2.5 × ULN
5. Adequate renal function as defined as defined by serum creatinine <1.5 x ULN
6. Adequate pancreatic function as defined by serum lipase and amylase ≤1.5 × ULN
Exclusion Criteria:
1. Received prior imatinib therapy
2. Received prior dasatinib therapy
3. Received prior nilotinib therapy
4. Received, for CML, any other systemic anticancer therapy, experimental therapy, or
radiation therapy with the exception of anagrelide or hydroxyurea
5. Major surgery within 28 days prior to initiating therapy
6. History of bleeding disorder unrelated to CML
7. History of acute pancreatitis within 1 year of study or history of chronic
pancreatitis
8. History of alcohol abuse
9. Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
10. Clinically significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to:
1. Myocardial infarction, within 6 months prior to randomization
2. Unstable angina within 6 months prior to randomization
3. Congestive heart failure within 6 months prior to randomization
4. History of clinically significant (as determined by the treating physician)
atrial arrhythmia or any ventricular arrhythmia
5. Any history of ventricular arrhythmia
6. Cerebrovascular accident or transient ischemic attack within 6 months prior to
randomization
7. Any history of peripheral arterial occlusive disease requiring revascularization
8. Any history of venous thromboembolism including deep venous thrombosis or
pulmonary embolism
11. Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg).
Patients with hypertension should be under treatment on study entry to effect blood
pressure control
12. Taking medications that are known to be associated with Torsades de Pointes
13. Ongoing or active infection. The requirement for intravenous (IV) antibiotics is
considered active infection
14. Known history of human immunodeficiency virus (HIV). Testing is not required in the
absence of history
15. Pregnant or breastfeeding
16. Malabsorption syndrome or other gastrointestinal illness that could affect oral
absorption of study drugs
17. Diagnosed with or received anticancer therapy for another primary malignancy within 3
years prior to entry (except for non-melanoma skin cancer or cervical cancer in situ)
18. Any condition or illness that, in the opinion of the Investigator, would compromise
patient safety or interfere with the evaluation of the drug
We found this trial at
66
sites
Memorial Sloan-Kettering Cancer Center Memorial Sloan-Kettering Cancer Center — the world's oldest and largest private...
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University of Chicago One of the world's premier academic and research institutions, the University of...
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Baylor College of Medicine Baylor College of Medicine in Houston, the only private medical school...
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Beth Israel Med Ctr The physicians and staff of Mount Sinai Beth Israel's Heart Institute...
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Mount Sinai School of Medicine Icahn School of Medicine at Mount Sinai is proud to...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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Seattle Cancer Care Alliance Seattle Cancer Care Alliance (SCCA) is a cancer treatment center that...
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New York Medical College The College was founded in 1860 by a group of New...
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1500 E Medical Center Dr
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
(734) 936-4000
University of Michigan Health System The University of Michigan is home to one of the...
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Greater Baltimore Medical Center The 255-bed medical center (acute and sub-acute care) is located on...
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22 South Greene Street
Baltimore, Maryland 21201
Baltimore, Maryland 21201
410-328-7904
University of Maryland Greenebaum Cancer Center The University of Maryland Marlene and Stewart Greenebaum Cancer...
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171 Ashley Avenue
Charleston, South Carolina 29425
Charleston, South Carolina 29425
843-792-1414
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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1969 W Ogden Ave
Chicago, Illinois 60612
Chicago, Illinois 60612
(312) 864-6000
John H. Stroger, Jr. Hospital of Cook County The Level 1 Trauma Center is one...
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University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
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University of Iowa Hospitals and Clinics University of Iowa Hospitals and Clinics—recognized as one of...
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University of Wisconsin In achievement and prestige, the University of Wisconsin–Madison has long been recognized...
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Winthrop University Hospital Founded in 1896 by a group of local physicians and concerned citizens,...
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West Virginia University West Virginia University, founded in 1867, has a long and rich history...
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3322 West End Avenue
Nashville, Tennessee 37203
Nashville, Tennessee 37203
(615)329-SCRI (7274)
Sarah Cannon Research Institute Sarah Cannon Research Institute (SCRI) is a global strategic research organization...
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Weill Medical College of Cornell University Founded in 1898, and affiliated with what is now...
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University of Oklahoma The OU Health Sciences Center is composed of seven health-related colleges located...
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Western Pennsylvania Hospital Featuring 308 private patient beds, West Penn Hospital has served Bloomfield and...
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2000 Circle of Hope Dr
Salt Lake City, Utah 84112
Salt Lake City, Utah 84112
(801) 585-0303
Huntsman Cancer Institute at University of Utah Huntsman Cancer Institute (HCI) is part of the...
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Siouxland Hematology-Oncology Associates, LLP Siouxland Hematology-Oncology Associates (SHOA) provides medical oncology treatment. In addition to...
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