Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)
- Conditions
- Chronic Myeloid Leukemia
- Interventions
- Registration Number
- NCT01650805
- Lead Sponsor
- Ariad Pharmaceuticals
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 307
-
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
-
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
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
-
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
-
Adequate renal function as defined as defined by serum creatinine <1.5 x ULN
-
Adequate pancreatic function as defined by serum lipase and amylase ≤1.5 × ULN
-
Received prior imatinib therapy
-
Received prior dasatinib therapy
-
Received prior nilotinib therapy
-
Received, for CML, any other systemic anticancer therapy, experimental therapy, or radiation therapy with the exception of anagrelide or hydroxyurea
-
Major surgery within 28 days prior to initiating therapy
-
History of bleeding disorder unrelated to CML
-
History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
-
History of alcohol abuse
-
Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
-
Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- Myocardial infarction, within 6 months prior to randomization
- Unstable angina within 6 months prior to randomization
- Congestive heart failure within 6 months prior to randomization
- History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia
- Any history of ventricular arrhythmia
- Cerebrovascular accident or transient ischemic attack within 6 months prior to randomization
- Any history of peripheral arterial occlusive disease requiring revascularization
- Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism
-
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
-
Taking medications that are known to be associated with Torsades de Pointes
-
Ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection
-
Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history
-
Pregnant or breastfeeding
-
Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drugs
-
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)
-
Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ponatinib ponatinib - imatinib imatinib (Gleevec/ Glivec) -
- Primary Outcome Measures
Name Time Method Major Molecular Response (MMR) Rate at 12 Months 12 months after first dose A ratio of reverse transcribed transcript of BCR-ABL to ABL ≤ 0.1% on the international scale, measured by real-time quantitative polymerase chain reaction.
- Secondary Outcome Measures
Name Time Method MMR Rate 5 years after first dose To compare the efficacy of ponatinib with imatinib, as measured by MMR rate, at 5 years
<10% BCR-ABL^IS Rate 3 months after first dose To compare the proportion of patients achieving a ratio of \<10% BCR-ABL to ABL transcript levels at 3 months, as measured by the international scale (\<10% BCR-ABL\^IS), in patients administered ponatinib versus those administered imatinib
Complete Cytogenetic Response (CCyR) Rate 12 months after first dose The percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. Responses are defined as follows: Complete (CCyR): 0% Ph+ metaphases.
Progression-free Survival Up to 8 years after the last patient's first dose To compare, according to treatment with ponatinib versus imatinib, progression-free survival
Overall Survival Up to 8 years after the last patient's first dose To compare, according to treatment with ponatinib versus imatinib, overall survival
Trial Locations
- Locations (170)
US Oncology - Providence Health System, Site #167
🇺🇸Burbank, California, United States
UCLA Department of Medicine, Site #027
🇺🇸Los Angeles, California, United States
Seattle Cancer Care Alliance, Site #100
🇺🇸Seattle, Washington, United States
Baylor College of Medicine, Site #063
🇺🇸Houston, Texas, United States
Bay Area Cancer Research Group, Site #156
🇺🇸Pleasant Hill, California, United States
Rocky Mountain Cancer Centers, Site #191
🇺🇸Boulder, Colorado, United States
Cancer Center of Central Connecticut, Site #147
🇺🇸Southington, Connecticut, United States
University Cancer Institute, Site #149
🇺🇸Boynton Beach, Florida, United States
Florida Cancer Specialists, Site #180
🇺🇸Fort Meyers, Florida, United States
John H. Stroger, Jr. Hospital of Cook County, Site #192
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital, Site #047
🇺🇸Boston, Massachusetts, United States
University of Massachusetts Worcester, Site #152
🇺🇸Worcester, Massachusetts, United States
Nebraska Hematology-Oncology, P.C., Site # 133
🇺🇸Lincoln, Nebraska, United States
Dana Farber Cancer Institute, Site #008
🇺🇸Boston, Massachusetts, United States
Mercy Clinic - Cancer & Hematology, Site #151
🇺🇸Springfield, Missouri, United States
Oncology Research Park Nicollet Institute, Site #195
🇺🇸St. Louis Park, Minnesota, United States
Mount Sinai School of Medicine, Site #189
🇺🇸New York, New York, United States
Signal Point Clinical Research Center, Site #139
🇺🇸Middletown, Ohio, United States
New York Medical College, Site #146
🇺🇸Valhalla, New York, United States
Associates in Oncology & Hematology, Site #186
🇺🇸Chattanooga, Tennessee, United States
US Oncology - Texas Oncology Dallas, Site #171
🇺🇸Dallas, Texas, United States
West Virginia University, Site #154
🇺🇸Morgantown, West Virginia, United States
University of Wisconsin, Site #030
🇺🇸Madison, Wisconsin, United States
Canberra Hospital, Site #971
🇦🇺Garran, Australian Capital Territory, Australia
Green Bay Oncology, Ltd. / St. Mary's Hospital Medical Center, Site #193
🇺🇸Green Bay, Wisconsin, United States
Jewish General Hospital, Site #129
🇨🇦Montreal, Quebec, Canada
UZ Gent - Department Hematology, Site #756
🇧🇪Gent, Belgium
University Health Network, Princess Margaret Hospital, Site #083
🇨🇦Toronto, Ontario, Canada
Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika, Site #514
🇨🇿Brno, Czech Republic
Ustav hematologie a krevni transfuse, Site #516
🇨🇿Praha, Czech Republic
CHU Henri Mondor, Site #520
🇫🇷Creteil Cedex, France
Hospital Claude Huriez, Site #952
🇫🇷Lille Cedex, France
Institut Paoli Calmette, Site #519
🇫🇷Marseille, France
CHU de Brabois, Site #953
🇫🇷Nancy Cedex, France
Hopital Saint-Louis, Site #957
🇫🇷Paris, France
CHU Purpan, Site #955
🇫🇷Toulouse Cedex, France
Universitätsklinikum Aachen, AÖR, Site #513
🇩🇪Aachen, Germany
Universitatsklinikum Freiburg, Site #527
🇩🇪Freiburg, Germany
Klinikum rechts der Isar, Site #949
🇩🇪Munchen, Germany
Ospedale Niguarda Ca' Granda di Milano, Site #531
🇮🇹Milan, Italy
U.O.C Ematologia con trapianto di midollo osseo, Site #560
🇮🇹Napoli, Italy
SCDU Medicina Interna II - Indirizzo Ematologico, Site #785
🇮🇹Orbassano, Italy
Dipartimento di Biotecnologie Cellulari ed Ematologia Universita La Sapienza - Policlinico Umberto I, Site #511
🇮🇹Rome, Italy
U.O. di Ematologia - Ospedale S. Eugenio, Site #962
🇮🇹Rome, Italy
The Catholic University of Korea, Site #938
🇰🇷Seocho-gu, Seoul, Korea, Republic of
Malopolskie Centrum Medyczne, Site #546
🇵🇱Krakow, Poland
Auckland City Hospital, Site #921
🇳🇿Grafton, Auckland, New Zealand
Hospital Universitari Son Espases, Site #553
🇪🇸Islas Baleares, Spain
Katedra i Klinika Hematologii, Site #547
🇵🇱Wroclaw, Poland
Instituto Portugues de Oncologia, Site #545
🇵🇹Lisboa, Portugal
Fundacion de Investigacion de Diego, Site #199
🇵🇷San Juan, Puerto Rico
Narodny onkologicky ustav, Site #532
🇸🇰Bratislava, Slovakia
Hospital Universitario La Princesa, Site #555
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario A Coruna, Hospital "Teresa Herrera," Site #554
🇪🇸A Coruna, Spain
Institut Catala d' Oncologia de Girona, S. de Hematologia Clinica, Site #734
🇪🇸Girona, Spain
Hospital Clinic, Site #963
🇪🇸Barcelona, Spain
Hospital Universitari Germans Trias i Pujol, Site #512
🇪🇸Badalona, Spain
Hospital Gregorio Maranon, Site #536
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca, Site #965
🇪🇸Salamanca, Spain
Skane University Hospital, Site #944
🇸🇪Lund, Sweden
Hospital Universitario Central de Asturias, Site #535
🇪🇸Oviedo, Spain
Uppsala University Hospital, Site #945
🇸🇪Uppsala, Sweden
Karolinska University Hospital Solna, Site #763
🇸🇪Stockholm, Sweden
Kantonsspital Aarau, Site #541
🇨🇭Aarau, Switzerland
Oxford University Hospitals NHS Trust, Site #543
🇬🇧Oxford, United Kingdom
Nottingham University Hospitals NHS Trust, Site #968
🇬🇧Nottingham, United Kingdom
US Oncology - Cancer Center of Kansas, Site #168
🇺🇸Wichita, Kansas, United States
Oddzial Hematologii, Site #551
🇵🇱Rzeszow, Poland
Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Medyczne, Site #548
🇵🇱Gdansk, Poland
Singapore General Hospital, Site #939
🇸🇬Singapore, Singapore
Univerzitna nemocnica Martin, Site #533
🇸🇰Martin, Slovakia
Medizinische Universitat Wien / AKH, Universitatsklinik fur Inniere Medizin I, Site #561
🇦🇹Wien, Austria
Kantonsspital St. Gallen, Site #707
🇨🇭St Gallen, Switzerland
Kaohsiung Chang Gung Memorial Hospital, Site #980
🇨🇳Kaohsiung, Taiwan
Bay Area Cancer Research Group, Site #157
🇺🇸Pleasant Hill, California, United States
Emory University, Site #058
🇺🇸Atlanta, Georgia, United States
Christiana Care Health Services, Site #155
🇺🇸Newark, Delaware, United States
Siouxland Hematology-Oncology Associates, Site #198
🇺🇸Sioux City, Iowa, United States
University of Chicago, Site #001
🇺🇸Chicago, Illinois, United States
Franciscan St. Francis Health, Site #138
🇺🇸Indianapolis, Indiana, United States
Loyola University Chicago, Site #054
🇺🇸Maywood, Illinois, United States
University of Maryland, Greenebaum Cancer Center, Site #040
🇺🇸Baltimore, Maryland, United States
Greater Baltimore Medical Center, Site #140
🇺🇸Baltimore, Maryland, United States
St. Agnes Healthcare, Site #185
🇺🇸Baltimore, Maryland, United States
Willis-Knighton Cancer Center, Site #196
🇺🇸Shreveport, Louisiana, United States
Providence Cancer Institute, Site #197
🇺🇸Southfield, Michigan, United States
Winthrop University Hospital, Site #153
🇺🇸Mineola, New York, United States
Memorial Sloan-Kettering Cancer Center, Site #078
🇺🇸New York, New York, United States
John Theurer Cancer Center, Site #128
🇺🇸Hackensack, New Jersey, United States
University of New Mexico Cancer Center, Site #166
🇺🇸Albuquerque, New Mexico, United States
Sarah Cannon Research Institute, Site #076
🇺🇸Nashville, Tennessee, United States
Providence Cancer Center Oncology and Hematology Care Eastside, Site #194
🇺🇸Portland, Oregon, United States
US Oncology - Texas Oncology Midland, Site #173
🇺🇸Midland, Texas, United States
Beth Israel Medical Center, Site #145
🇺🇸New York, New York, United States
Southeastern Medical Oncology Center, Site #188
🇺🇸Goldsboro, North Carolina, United States
University of Oklahoma, Site #028
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University, Site #048
🇺🇸Portland, Oregon, United States
Kaiser Permanente Northwest, Site #200
🇺🇸Portland, Oregon, United States
Carolina Hematology Oncology, Site #143
🇺🇸Sumter, South Carolina, United States
University of Texas Southwestern Medical Center, Site #178
🇺🇸Dallas, Texas, United States
Box Hill Hospital, Site #940
🇦🇺Melbourne, Victoria, Australia
Royal Perth Hospital, Site #972
🇦🇺Perth, Western Australia, Australia
Helsinki University Central Hospital, Site #542
🇫🇮Helsinki, Finland
US Oncology - Cancer Care Center of South Texas, Site #170
🇺🇸San Antonio, Texas, United States
The Peter MacCallum Cancer Center, Site #950
🇦🇺East Melbourne, Victoria, Australia
Clinique Universitaire de Saint-Luc, Department of Haematology, Site #508
🇧🇪Bruxelles, Belgium
Royal Adelaide Hospital, Site #951
🇦🇺Adelaide, South Australia, Australia
UZ Brussel - Department Hematology, Site #544
🇧🇪Brussel, Belgium
UZ Gasthuisberg - Department of Hematology, Site #700
🇧🇪Leuven, Belgium
Fakultni nemocnice Olomouc, Hematoonkologicka klinika, Site #515
🇨🇿Olomouc, Czech Republic
CHRU de Brest, Hopital Morvan, Site #523
🇫🇷Brest, France
Prince of Wales Hospital, Site #974
🇭🇰Hong Kong, Hong Kong
Universitatsklinikum Hamburg-Eppendorf, Site #524
🇩🇪Hamburg, Germany
Universitatsklinikum Jena, Site #946
🇩🇪Jena, Germany
Institut Bergonie, Site #772
🇫🇷Bordeaux, France
Centre Hospitalier de Versailles, Site #958
🇫🇷Le Chesnay Cedex, France
FN Hradec Kralove, Site #517
🇨🇿Hradec Kralove, Czech Republic
CHU de Nantes, Site #521
🇫🇷Nantes Cedex, France
Service Hematologie - Hospital Archet I, Site #509
🇫🇷Nice Cedex, France
Centre Hospitalier Lyon Sud, Site #956
🇫🇷Pierre Benite, France
CHU de Poitiers, Site #954
🇫🇷Poitiers, France
Hospital Saint Antoine, Site #518
🇫🇷Paris, France
Unita Operativa di Ematologia con Trapianto, Site #529
🇮🇹Bari, Italy
Istituto di Ematologia "L. & A. Seragnoli", Site #959
🇮🇹Bologna, Italy
Charite - Universitatsmedizin Berlin, Site #701
🇩🇪Berlin, Germany
Universitatsklinikum Koln-AOR, Site #525
🇩🇪Koln, Germany
A.O. Universitaria Policlinico Vittorio Emanuele di Catania, Site #530
🇮🇹Catania, Italy
Clinica Ematologica, Site #528
🇮🇹Genova, Italy
S.C. Ematologia, Site #960
🇮🇹Modena, Italy
San Gerardo Hospital, Site #961
🇮🇹Monza, Italy
Universita Federico II, Site #510
🇮🇹Napoli, Italy
VU Medical Centre - Department Haematology, Site #948
🇳🇱Amsterdam, Netherlands
Christchurch Hospital, Site #922
🇳🇿Christchurch, New Zealand
Waikato Hospital, Site #977
🇳🇿Hamilton, New Zealand
Klinika Hematologii Wojewodzkiego Szpitala Specjalistycznego, Site #550
🇵🇱Lodz, Poland
H.U. Ramon y Cajal, Site #538
🇪🇸Madrid, Spain
Hospital La Paz, Site #966
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre, Site #537
🇪🇸Madrid, Spain
Karolinska University Hospital Huddinge, Site #534
🇸🇪Stockholm, Sweden
Kent and Medway Cancer Research Network, Site #558
🇬🇧Gillingham, United Kingdom
Hospital Clinico Universitario de Valencia, Site #964
🇪🇸Valencia, Spain
China Medical University Hospital, Site #978
🇨🇳Taiching, Taiwan
National Taiwan University Hospital, Site #979
🇨🇳Taipei, Taiwan
Hammersmith Hospital, Site #967
🇬🇧London, United Kingdom
Western General Hospital, Site #556
🇬🇧Edinburgh, United Kingdom
University of Glasgow, Site #797
🇬🇧Glasgow, United Kingdom
St. James University Hospital, Site #540
🇬🇧Leeds, United Kingdom
Royal Liverpool University Hospital, Site #969
🇬🇧Liverpool, United Kingdom
Norfolk & Norwich University Hospital Foundation Trust, Site #557
🇬🇧Norwich, United Kingdom
Newcastle University, Site #970
🇬🇧Newcastle, United Kingdom
Huntsman Cancer Institute, Site #043
🇺🇸Salt Lake City, Utah, United States
Royal North Shore Hospital, Site #941
🇦🇺Sydney, New South Wales, Australia
Weill Cornell Medical College, Site #006
🇺🇸New York, New York, United States
North Shore Hospital, Site #976
🇳🇿Takapuna, New Zealand
US Oncology - Comprehensive Cancer Center of Nevada, Site #169
🇺🇸Las Vegas, Nevada, United States
Universitat Heidelberg, CML - Studienzentrale III. Medizinische Klinik, Site #947
🇩🇪Mannheim, Germany
Florida Cancer Specialists, Site #179
🇺🇸St. Petersburg, Florida, United States
University of Iowa Hospitals and Clinics, Site #050
🇺🇸Iowa City, Iowa, United States
Maimonides Cancer Center, Site #177
🇺🇸Brooklyn, New York, United States
Western Pennsylvania Hospital, Site #159
🇺🇸Pittsburgh, Pennsylvania, United States
Gettysburg Cancer Center, Site #160
🇺🇸Gettysburg, Pennsylvania, United States
Universitatsklinikum Carl Gustav Carus an der TU Dresden, Site #526
🇩🇪Dresden, Germany
US Oncology - Northwest Cancer Specialists, Site #174
🇺🇸Vancouver, Washington, United States
University of Michigan Medical Center, Site #011
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic, Site #044
🇺🇸Rochester, Minnesota, United States
Saint Luke's Hospital, Site #162
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina, Site #148
🇺🇸Charleston, South Carolina, United States
US Oncology - Texas Oncology Austin, Site #172
🇺🇸Austin, Texas, United States
VCU Massey Cancer Center, Dalton Oncology Clinic, Site #069
🇺🇸Richmond, Virginia, United States
Queen Mary Hospital, Site #973
🇭🇰Hong Kong, Hong Kong