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A Phase 3 Randomized,Open-Label Study of Ponatinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase

Phase 3
18 Years
Open (Enrolling)
Chronic Myeloid Leukemia

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Trial Information

A Phase 3 Randomized,Open-Label Study of Ponatinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Myeloid Leukemia in 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

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

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

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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Major Molecular response (MMR) rate

Outcome Description:

To compare the efficacy of ponatinib with imatinib as measured by major molecular response (MMR) rate at 12 months (1 month or cycle = 28 days)

Outcome Time Frame:

12 months after first dose

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

June 2012

Completion Date:

June 2021

Related Keywords:

  • Chronic Myeloid Leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Neoplasms by Histologic Type
  • Neoplasms
  • Lymphoproliferative Disorders
  • Lymphatic Diseases
  • Immunoproliferative Disorders
  • Immune System Diseases
  • Myeloproliferative Disorders
  • Bone Marrow Diseases
  • Hematologic Diseases
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive



Memorial Sloan-Kettering Cancer Center, Site #078New York, New York  10065
Franciscan St. Francis Health, Site #138Indianapolis, Indiana  46237
Nebraska Hematology-Oncology, P.C., Site # 133Lincoln, Nebraska  68506
Mayo Clinic, Site #044Rochester, Minnesota  55905
Medical University of South Carolina, Site #148Charleston, South Carolina  29425
Seattle Cancer Care Alliance, Site #100Seattle, Washington  98109
US Oncology - Providence Health System, Site #167Burbank, California  91505
UCLA Department of Medicine, Site #027Los Angeles, California  90095
Bay Area Cancer Research Group, Site #157Pleasant Hill, California  94523
Bay Area Cancer Research Group, Site #156Pleasant Hill, California  94523
Rocky Mountain Cancer Centers, Site #191Boulder, Colorado  80303
Cancer Center of Central Connecticut, Site #147Southington, Connecticut  06489
Christiana Care Health Services, Site #155Newark, Delaware  19713
University Cancer Institute, Site #149Boynton Beach, Florida  33426
Florida Cancer Specialists, Site #180Fort Meyers, Florida  33916
Florida Cancer Specialists, Site #179St. Petersburg, Florida  33705
Emory University, Site #058Atlanta, Georgia  30322
University of Chicago, Site #001Chicago, Illinois  60637
Loyola University Chicago, Site #054Maywood, Illinois  60153
University of Iowa Hospitals and Clinics, Site #050Iowa City, Iowa  52242
US Oncology - Cancer Center of Kansas, Site #168Wichita, Kansas  67214
Greater Baltimore Medical Center, Site #140Baltimore, Maryland  21204
University of Maryland, Greenebaum Cancer Center, Site #040Baltimore, Maryland  21201
Dana Farber Cancer Institute, Site #008Boston, Massachusetts  02215
Massachusetts General Hospital, Site #047Boston, Massachusetts  02114
University of Michigan Medical Center, Site #011Ann Arbor, Michigan  48109
Saint Luke's Hospital, Site #162Kansas City, Missouri  64111
Mercy Clinic - Cancer & Hematology, Site #151Springfield, Missouri  65804
US Oncology - Comprehensive Cancer Center of Nevada, Site #169Las Vegas, Nevada  89169
John Theurer Cancer Center, Site #128Hackensack, New Jersey  07601
University of New Mexico Cancer Center, Site #166Albuquerque, New Mexico  87106
Winthrop University Hospital, Site #153Mineola, New York  11501
Weill Cornell Medical College, Site #006New York, New York  10065
New York Medical College, Site #146Valhalla, New York  10595
Signal Point Clinical Research Center, Site #139Middletown, Ohio  45042
University of Oklahoma, Site #028Oklahoma City, Oklahoma  73104
Oregon Health & Science University, Site #048Portland, Oregon  97239
Gettysburg Cancer Center, Site #160Gettysburg, Pennsylvania  17325
Western Pennsylvania Hospital, Site #159Pittsburgh, Pennsylvania  15224
Carolina Hematology Oncology, Site #143Sumter, South Carolina  29150
Sarah Cannon Research Institute, Site #076Nashville, Tennessee  37203
US Oncology - Texas Oncology Austin, Site #172Austin, Texas  78705
US Oncology - Texas Oncology Dallas, Site #171Dallas, Texas  75231
US Oncology - Texas Oncology Midland, Site #173Midland, Texas  79701
US Oncology - Cancer Care Center of South Texas, Site #170San Antonio, Texas  78229
Huntsman Cancer Institute, Site #043Salt Lake City, Utah  84112
US Oncology - Northwest Cancer Specialists, Site #174Vancouver, Washington  98684
West Virginia University, Site #154Morgantown, West Virginia  26506