Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)
NCT ID: NCT01650805
Last Updated: 2014-11-17
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
307 participants
INTERVENTIONAL
2012-06-30
2013-10-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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ponatinib
ponatinib
45 mg tablet, taken orally once daily
imatinib
imatinib (Gleevec/ Glivec)
400 mg tablet, taken orally once daily
Interventions
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ponatinib
45 mg tablet, taken orally once daily
imatinib (Gleevec/ Glivec)
400 mg tablet, taken orally once daily
Eligibility Criteria
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Inclusion Criteria
* 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
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
18 Years
ALL
No
Sponsors
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Ariad Pharmaceuticals
INDUSTRY
Responsible Party
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Locations
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US Oncology - Providence Health System, Site #167
Burbank, California, United States
UCLA Department of Medicine, Site #027
Los Angeles, California, United States
Bay Area Cancer Research Group, Site #156
Pleasant Hill, California, United States
Bay Area Cancer Research Group, Site #157
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
Christiana Care Health Services, Site #155
Newark, Delaware, United States
University Cancer Institute, Site #149
Boynton Beach, Florida, United States
Florida Cancer Specialists, Site #180
Fort Meyers, Florida, United States
Florida Cancer Specialists, Site #179
St. Petersburg, Florida, United States
Emory University, Site #058
Atlanta, Georgia, United States
John H. Stroger, Jr. Hospital of Cook County, Site #192
Chicago, Illinois, United States
University of Chicago, Site #001
Chicago, Illinois, United States
Loyola University Chicago, Site #054
Maywood, Illinois, United States
Franciscan St. Francis Health, Site #138
Indianapolis, Indiana, United States
University of Iowa Hospitals and Clinics, Site #050
Iowa City, Iowa, United States
Siouxland Hematology-Oncology Associates, Site #198
Sioux City, Iowa, United States
US Oncology - Cancer Center of Kansas, Site #168
Wichita, Kansas, United States
Willis-Knighton Cancer Center, Site #196
Shreveport, Louisiana, 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
Massachusetts General Hospital, Site #047
Boston, Massachusetts, United States
Dana Farber Cancer Institute, Site #008
Boston, Massachusetts, United States
University of Massachusetts Worcester, Site #152
Worcester, Massachusetts, United States
University of Michigan Medical Center, Site #011
Ann Arbor, Michigan, United States
Providence Cancer Institute, Site #197
Southfield, Michigan, United States
Mayo Clinic, Site #044
Rochester, Minnesota, United States
Oncology Research Park Nicollet Institute, Site #195
Saint Louis Park, Minnesota, United States
Saint Luke's Hospital, Site #162
Kansas City, Missouri, United States
Mercy Clinic - Cancer & Hematology, Site #151
Springfield, Missouri, United States
Nebraska Hematology-Oncology, P.C., Site # 133
Lincoln, Nebraska, United States
US Oncology - Comprehensive Cancer Center of Nevada, Site #169
Las Vegas, Nevada, 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
Maimonides Cancer Center, Site #177
Brooklyn, New York, United States
Winthrop University Hospital, Site #153
Mineola, New York, United States
Beth Israel Medical Center, Site #145
New York, New York, United States
Mount Sinai School of Medicine, Site #189
New York, New York, United States
Memorial Sloan-Kettering Cancer Center, Site #078
New York, New York, United States
Weill Cornell Medical College, Site #006
New York, New York, United States
New York Medical College, Site #146
Valhalla, New York, United States
Southeastern Medical Oncology Center, Site #188
Goldsboro, North Carolina, United States
Signal Point Clinical Research Center, Site #139
Middletown, Ohio, United States
University of Oklahoma, Site #028
Oklahoma City, Oklahoma, United States
Providence Cancer Center Oncology and Hematology Care Eastside, Site #194
Portland, Oregon, United States
Kaiser Permanente Northwest, Site #200
Portland, Oregon, United States
Oregon Health & Science University, Site #048
Portland, Oregon, United States
Gettysburg Cancer Center, Site #160
Gettysburg, Pennsylvania, United States
Western Pennsylvania Hospital, Site #159
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina, Site #148
Charleston, South Carolina, United States
Carolina Hematology Oncology, Site #143
Sumter, South Carolina, United States
Associates in Oncology & Hematology, Site #186
Chattanooga, Tennessee, United States
Sarah Cannon Research Institute, Site #076
Nashville, Tennessee, United States
US Oncology - Texas Oncology Austin, Site #172
Austin, Texas, United States
US Oncology - Texas Oncology Dallas, Site #171
Dallas, Texas, United States
University of Texas Southwestern Medical Center, Site #178
Dallas, Texas, United States
Baylor College of Medicine, Site #063
Houston, Texas, United States
US Oncology - Texas Oncology Midland, Site #173
Midland, Texas, United States
US Oncology - Cancer Care Center of South Texas, Site #170
San Antonio, Texas, United States
Huntsman Cancer Institute, Site #043
Salt Lake City, Utah, United States
VCU Massey Cancer Center, Dalton Oncology Clinic, Site #069
Richmond, Virginia, United States
Seattle Cancer Care Alliance, Site #100
Seattle, Washington, United States
US Oncology - Northwest Cancer Specialists, Site #174
Vancouver, Washington, United States
West Virginia University, Site #154
Morgantown, West Virginia, United States
Green Bay Oncology, Ltd. / St. Mary's Hospital Medical Center, Site #193
Green Bay, Wisconsin, United States
University of Wisconsin, Site #030
Madison, Wisconsin, United States
Canberra Hospital, Site #971
Garran, Australian Capital Territory, Australia
Royal North Shore Hospital, Site #941
Sydney, New South Wales, Australia
Royal Adelaide Hospital, Site #951
Adelaide, South Australia, Australia
The Peter MacCallum Cancer Center, Site #950
East Melbourne, Victoria, Australia
Box Hill Hospital, Site #940
Melbourne, Victoria, Australia
Royal Perth Hospital, Site #972
Perth, Western Australia, Australia
Medizinische Universitat Wien / AKH, Universitatsklinik fur Inniere Medizin I, Site #561
Vienna, , Austria
Clinique Universitaire de Saint-Luc, Department of Haematology, Site #508
Brussels, , Belgium
UZ Brussel - Department Hematology, Site #544
Brussels, , Belgium
UZ Gent - Department Hematology, Site #756
Ghent, , Belgium
UZ Gasthuisberg - Department of Hematology, Site #700
Leuven, , Belgium
University Health Network, Princess Margaret Hospital, Site #083
Toronto, Ontario, Canada
Jewish General Hospital, Site #129
Montreal, Quebec, Canada
Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika, Site #514
Brno, , Czechia
FN Hradec Kralove, Site #517
Hradec Králové, , Czechia
Fakultni nemocnice Olomouc, Hematoonkologicka klinika, Site #515
Olomouc, , Czechia
Ustav hematologie a krevni transfuse, Site #516
Prague, , Czechia
Helsinki University Central Hospital, Site #542
Helsinki, , Finland
Institut Bergonie, Site #772
Bordeaux, , France
CHRU de Brest, Hopital Morvan, Site #523
Brest, , France
CHU Henri Mondor, Site #520
Créteil, , France
Centre Hospitalier de Versailles, Site #958
Le Chesnay, , France
Hospital Claude Huriez, Site #952
Lille, , France
Institut Paoli Calmette, Site #519
Marseille, , France
CHU de Brabois, Site #953
Nancy, , France
CHU de Nantes, Site #521
Nantes, , France
Service Hematologie - Hospital Archet I, Site #509
Nice, , France
Hopital Saint-Louis, Site #957
Paris, , France
Hospital Saint Antoine, Site #518
Paris, , France
Centre Hospitalier Lyon Sud, Site #956
Pierre-Bénite, , France
CHU de Poitiers, Site #954
Poitiers, , France
CHU Purpan, Site #955
Toulouse, , France
Universitätsklinikum Aachen, AÖR, Site #513
Aachen, , Germany
Charite - Universitatsmedizin Berlin, Site #701
Berlin, , Germany
Universitatsklinikum Koln-AOR, Site #525
Cologne, , Germany
Universitatsklinikum Carl Gustav Carus an der TU Dresden, Site #526
Dresden, , Germany
Universitatsklinikum Freiburg, Site #527
Freiburg im Breisgau, , Germany
Universitatsklinikum Hamburg-Eppendorf, Site #524
Hamburg, , Germany
Universitatsklinikum Jena, Site #946
Jena, , Germany
Universitat Heidelberg, CML - Studienzentrale III. Medizinische Klinik, Site #947
Mannheim, , Germany
Klinikum rechts der Isar, Site #949
München, , Germany
Prince of Wales Hospital, Site #974
Hong Kong, , Hong Kong
Queen Mary Hospital, Site #973
Hong Kong, , Hong Kong
Unita Operativa di Ematologia con Trapianto, Site #529
Bari, , Italy
Istituto di Ematologia "L. & A. Seragnoli", Site #959
Bologna, , Italy
A.O. Universitaria Policlinico Vittorio Emanuele di Catania, Site #530
Catania, , Italy
Clinica Ematologica, Site #528
Genova, , Italy
Ospedale Niguarda Ca' Granda di Milano, Site #531
Milan, , Italy
S.C. Ematologia, Site #960
Modena, , Italy
San Gerardo Hospital, Site #961
Monza, , Italy
U.O.C Ematologia con trapianto di midollo osseo, Site #560
Napoli, , Italy
Universita Federico II, Site #510
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
VU Medical Centre - Department Haematology, Site #948
Amsterdam, , Netherlands
Auckland City Hospital, Site #921
Grafton, Auckland, New Zealand
Christchurch Hospital, Site #922
Christchurch, , New Zealand
Waikato Hospital, Site #977
Hamilton, , New Zealand
North Shore Hospital, Site #976
Takapuna, , New Zealand
Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Medyczne, Site #548
Gdansk, , Poland
Malopolskie Centrum Medyczne, Site #546
Krakow, , Poland
Klinika Hematologii Wojewodzkiego Szpitala Specjalistycznego, Site #550
Lodz, , Poland
Oddzial Hematologii, Site #551
Rzeszów, , Poland
Katedra i Klinika Hematologii, Site #547
Wroclaw, , Poland
Instituto Portugues de Oncologia, Site #545
Lisbon, , Portugal
Fundacion de Investigacion de Diego, Site #199
San Juan, , Puerto Rico
Singapore General Hospital, Site #939
Singapore, , Singapore
Narodny onkologicky ustav, Site #532
Bratislava, , Slovakia
Univerzitna nemocnica Martin, Site #533
Martin, , Slovakia
The Catholic University of Korea, Site #938
Seocho-gu, Seoul, South Korea
Complejo Hospitalario Universitario A Coruna, Hospital "Teresa Herrera," Site #554
A Coruña, , Spain
Hospital Universitari Germans Trias i Pujol, Site #512
Badalona, , Spain
Hospital Clinic, Site #963
Barcelona, , Spain
Institut Catala d' Oncologia de Girona, S. de Hematologia Clinica, Site #734
Girona, , Spain
Hospital Universitari Son Espases, Site #553
Islas Baleares, , Spain
Hospital Universitario La Princesa, Site #555
Madrid, , Spain
Hospital Gregorio Maranon, Site #536
Madrid, , Spain
H.U. Ramon y Cajal, Site #538
Madrid, , Spain
Hospital Universitario 12 de Octubre, Site #537
Madrid, , Spain
Hospital La Paz, Site #966
Madrid, , Spain
Hospital Universitario Central de Asturias, Site #535
Oviedo, , Spain
Hospital Universitario de Salamanca, Site #965
Salamanca, , Spain
Hospital Clinico Universitario de Valencia, Site #964
Valencia, , Spain
Skane University Hospital, Site #944
Lund, , Sweden
Karolinska University Hospital Huddinge, Site #534
Stockholm, , Sweden
Karolinska University Hospital Solna, Site #763
Stockholm, , Sweden
Uppsala University Hospital, Site #945
Uppsala, , Sweden
Kantonsspital Aarau, Site #541
Aarau, , Switzerland
Kantonsspital St. Gallen, Site #707
Sankt Gallen, , Switzerland
Kaohsiung Chang Gung Memorial Hospital, Site #980
Kaohsiung City, , Taiwan
China Medical University Hospital, Site #978
Taiching, , Taiwan
National Taiwan University Hospital, Site #979
Taipei, , Taiwan
Western General Hospital, Site #556
Edinburgh, , United Kingdom
Kent and Medway Cancer Research Network, Site #558
Gillingham, , 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
Hammersmith Hospital, Site #967
London, , United Kingdom
Newcastle University, Site #970
Newcastle, , United Kingdom
Norfolk & Norwich University Hospital Foundation Trust, Site #557
Norwich, , United Kingdom
Nottingham University Hospitals NHS Trust, Site #968
Nottingham, , United Kingdom
Oxford University Hospitals NHS Trust, Site #543
Oxford, , United Kingdom
Countries
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References
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Hanley MJ, Diderichsen PM, Narasimhan N, Srivastava S, Gupta N, Venkatakrishnan K. Population Pharmacokinetics of Ponatinib in Healthy Adult Volunteers and Patients With Hematologic Malignancies and Model-Informed Dose Selection for Pediatric Development. J Clin Pharmacol. 2022 Apr;62(4):555-567. doi: 10.1002/jcph.1990. Epub 2021 Dec 16.
Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, Etienne G, Nicolini FE, le Coutre P, Clark RE, Stenke L, Andorsky D, Oehler V, Lustgarten S, Rivera VM, Clackson T, Haluska FG, Baccarani M, Cortes JE, Guilhot F, Hochhaus A, Hughes T, Kantarjian HM, Shah NP, Talpaz M, Deininger MW; EPIC investigators. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016 May;17(5):612-21. doi: 10.1016/S1470-2045(16)00080-2. Epub 2016 Apr 12.
Other Identifiers
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AP24534-12-301
Identifier Type: -
Identifier Source: org_study_id