Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)

NCT01650805 | Terminated Phase 3 Results DMC

• 1 other identifier: AP24534-12-301
• Study Type: interventional
• Target: 307
• Locations: 23 countries
• Sites: 169

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.

Conditions

Chronic Myeloid Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Major Molecular Response (MMR) Rate at 12 Months

  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.

  12 months after first dose

Secondary Outcomes (5)

• MMR Rate

  5 years after first dose

• <10% BCR-ABL^IS Rate

  3 months after first dose

• Complete Cytogenetic Response (CCyR) Rate

  12 months after first dose

• Progression-free Survival

  Up to 8 years after the last patient's first dose

• Overall Survival

  Up to 8 years after the last patient's first dose

Study Arms (2)

ponatinib

EXPERIMENTAL

Drug: ponatinib

imatinib

ACTIVE COMPARATOR

Drug: imatinib (Gleevec/ Glivec)

Interventions

ponatinib DRUG

45 mg tablet, taken orally once daily

ponatinib

imatinib (Gleevec/ Glivec) DRUG

400 mg tablet, taken orally once daily

imatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ariad Pharmaceuticals: lead

Study Sites (170)

US Oncology - Providence Health System, Site #167

Burbank, California, 91505, United States

Location

UCLA Department of Medicine, Site #027

Los Angeles, California, 90095, United States

Location

Bay Area Cancer Research Group, Site #156

Pleasant Hill, California, 94523, United States

Location

Bay Area Cancer Research Group, Site #157

Pleasant Hill, California, 94523, United States

Location

Rocky Mountain Cancer Centers, Site #191

Boulder, Colorado, 80303, United States

Location

Cancer Center of Central Connecticut, Site #147

Southington, Connecticut, 06489, United States

Location

Christiana Care Health Services, Site #155

Newark, Delaware, 19713, United States

Location

University Cancer Institute, Site #149

Boynton Beach, Florida, 33426, United States

Location

Florida Cancer Specialists, Site #180

Fort Meyers, Florida, 33916, United States

Location

Florida Cancer Specialists, Site #179

St. Petersburg, Florida, 33705, United States

Location

Emory University, Site #058

Atlanta, Georgia, 30322, United States

Location

John H. Stroger, Jr. Hospital of Cook County, Site #192

Chicago, Illinois, 60612, United States

Location

University of Chicago, Site #001

Chicago, Illinois, 60637, United States

Location

Loyola University Chicago, Site #054

Maywood, Illinois, 60153, United States

Location

Franciscan St. Francis Health, Site #138

Indianapolis, Indiana, 46237, United States

Location

University of Iowa Hospitals and Clinics, Site #050

Iowa City, Iowa, 52242, United States

Location

Siouxland Hematology-Oncology Associates, Site #198

Sioux City, Iowa, 51101, United States

Location

US Oncology - Cancer Center of Kansas, Site #168

Wichita, Kansas, 67214, United States

Location

Willis-Knighton Cancer Center, Site #196

Shreveport, Louisiana, 71103, United States

Location

University of Maryland, Greenebaum Cancer Center, Site #040

Baltimore, Maryland, 21201, United States

Location

Greater Baltimore Medical Center, Site #140

Baltimore, Maryland, 21204, United States

Location

St. Agnes Healthcare, Site #185

Baltimore, Maryland, 21229, United States

Location

Massachusetts General Hospital, Site #047

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute, Site #008

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Worcester, Site #152

Worcester, Massachusetts, 01655, United States

Location

University of Michigan Medical Center, Site #011

Ann Arbor, Michigan, 48109, United States

Location

Providence Cancer Institute, Site #197

Southfield, Michigan, 48075, United States

Location

Mayo Clinic, Site #044

Rochester, Minnesota, 55905, United States

Location

Oncology Research Park Nicollet Institute, Site #195

Saint Louis Park, Minnesota, 55426, United States

Location

Saint Luke's Hospital, Site #162

Kansas City, Missouri, 64111, United States

Location

Mercy Clinic - Cancer & Hematology, Site #151

Springfield, Missouri, 65804, United States

Location

Nebraska Hematology-Oncology, P.C., Site # 133

Lincoln, Nebraska, 68506, United States

Location

US Oncology - Comprehensive Cancer Center of Nevada, Site #169

Las Vegas, Nevada, 89169, United States

Location

John Theurer Cancer Center, Site #128

Hackensack, New Jersey, 07601, United States

Location

University of New Mexico Cancer Center, Site #166

Albuquerque, New Mexico, 87106, United States

Location

Maimonides Cancer Center, Site #177

Brooklyn, New York, 11220, United States

Location

Winthrop University Hospital, Site #153

Mineola, New York, 11501, United States

Location

Beth Israel Medical Center, Site #145

New York, New York, 10003, United States

Location

Mount Sinai School of Medicine, Site #189

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center, Site #078

New York, New York, 10065, United States

Location

Weill Cornell Medical College, Site #006

New York, New York, 10065, United States

Location

New York Medical College, Site #146

Valhalla, New York, 10595, United States

Location

Southeastern Medical Oncology Center, Site #188

Goldsboro, North Carolina, 27534, United States

Location

Signal Point Clinical Research Center, Site #139

Middletown, Ohio, 45042, United States

Location

University of Oklahoma, Site #028

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Cancer Center Oncology and Hematology Care Eastside, Site #194

Portland, Oregon, 97213, United States

Location

Kaiser Permanente Northwest, Site #200

Portland, Oregon, 97227, United States

Location

Oregon Health & Science University, Site #048

Portland, Oregon, 97239, United States

Location

Gettysburg Cancer Center, Site #160

Gettysburg, Pennsylvania, 17325, United States

Location

Western Pennsylvania Hospital, Site #159

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina, Site #148

Charleston, South Carolina, 29425, United States

Location

Carolina Hematology Oncology, Site #143

Sumter, South Carolina, 29150, United States

Location

Associates in Oncology & Hematology, Site #186

Chattanooga, Tennessee, 37421, United States

Location

Sarah Cannon Research Institute, Site #076

Nashville, Tennessee, 37203, United States

Location

US Oncology - Texas Oncology Austin, Site #172

Austin, Texas, 78705, United States

Location

US Oncology - Texas Oncology Dallas, Site #171

Dallas, Texas, 75231, United States

Location

University of Texas Southwestern Medical Center, Site #178

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine, Site #063

Houston, Texas, 77030, United States

Location

US Oncology - Texas Oncology Midland, Site #173

Midland, Texas, 79701, United States

Location

US Oncology - Cancer Care Center of South Texas, Site #170

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute, Site #043

Salt Lake City, Utah, 84112, United States

Location

VCU Massey Cancer Center, Dalton Oncology Clinic, Site #069

Richmond, Virginia, 23298, United States

Location

Seattle Cancer Care Alliance, Site #100

Seattle, Washington, 98109, United States

Location

US Oncology - Northwest Cancer Specialists, Site #174

Vancouver, Washington, 98684, United States

Location

West Virginia University, Site #154

Morgantown, West Virginia, 26506, United States

Location

Green Bay Oncology, Ltd. / St. Mary's Hospital Medical Center, Site #193

Green Bay, Wisconsin, 54303, United States

Location

University of Wisconsin, Site #030

Madison, Wisconsin, 53792, United States

Location

Canberra Hospital, Site #971

Garran, Australian Capital Territory, 2605, Australia

Location

Royal North Shore Hospital, Site #941

Sydney, New South Wales, 2065, Australia

Location

Royal Adelaide Hospital, Site #951

Adelaide, South Australia, 5000, Australia

Location

The Peter MacCallum Cancer Center, Site #950

East Melbourne, Victoria, 3002, Australia

Location

Box Hill Hospital, Site #940

Melbourne, Victoria, 3128, Australia

Location

Royal Perth Hospital, Site #972

Perth, Western Australia, 6000, Australia

Location

Medizinische Universitat Wien / AKH, Universitatsklinik fur Inniere Medizin I, Site #561

Vienna, 01090, Austria

Location

Clinique Universitaire de Saint-Luc, Department of Haematology, Site #508

Brussels, 3000, Belgium

Location

UZ Brussel - Department Hematology, Site #544

Brussels, Belgium

Location

UZ Gent - Department Hematology, Site #756

Ghent, Belgium

Location

UZ Gasthuisberg - Department of Hematology, Site #700

Leuven, 3000, Belgium

Location

University Health Network, Princess Margaret Hospital, Site #083

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital, Site #129

Montreal, Quebec, H3T 1E2, Canada

Location

Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika, Site #514

Brno, 62500, Czechia

Location

FN Hradec Kralove, Site #517

Hradec Králové, 50005, Czechia

Location

Fakultni nemocnice Olomouc, Hematoonkologicka klinika, Site #515

Olomouc, 77520, Czechia

Location

Ustav hematologie a krevni transfuse, Site #516

Prague, 12808, Czechia

Location

Helsinki University Central Hospital, Site #542

Helsinki, Finland

Location

Institut Bergonie, Site #772

Bordeaux, France

Location

CHRU de Brest, Hopital Morvan, Site #523

Brest, 29200, France

Location

CHU Henri Mondor, Site #520

Créteil, 94010, France

Location

Centre Hospitalier de Versailles, Site #958

Le Chesnay, France

Location

Hospital Claude Huriez, Site #952

Lille, 59037, France

Location

Institut Paoli Calmette, Site #519

Marseille, France

Location

CHU de Brabois, Site #953

Nancy, France

Location

CHU de Nantes, Site #521

Nantes, 44093, France

Location

Service Hematologie - Hospital Archet I, Site #509

Nice, 06202, France

Location

Hopital Saint-Louis, Site #957

Paris, 75475, France

Location

Hospital Saint Antoine, Site #518

Paris, France

Location

Centre Hospitalier Lyon Sud, Site #956

Pierre-Bénite, 69495, France

Location

CHU de Poitiers, Site #954

Poitiers, 86021, France

Location

CHU Purpan, Site #955

Toulouse, France

Location

Universitätsklinikum Aachen, AÖR, Site #513

Aachen, 52074, Germany

Location

Charite - Universitatsmedizin Berlin, Site #701

Berlin, 13353, Germany

Location

Universitatsklinikum Koln-AOR, Site #525

Cologne, 50937, Germany

Location

Universitatsklinikum Carl Gustav Carus an der TU Dresden, Site #526

Dresden, 01307, Germany

Location

Universitatsklinikum Freiburg, Site #527

Freiburg im Breisgau, Germany

Location

Universitatsklinikum Hamburg-Eppendorf, Site #524

Hamburg, 20246, Germany

Location

Universitatsklinikum Jena, Site #946

Jena, 07747, Germany

Location

Universitat Heidelberg, CML - Studienzentrale III. Medizinische Klinik, Site #947

Mannheim, 68167, Germany

Location

Klinikum rechts der Isar, Site #949

München, 81675, Germany

Location

Prince of Wales Hospital, Site #974

Hong Kong, Hong Kong

Location

Queen Mary Hospital, Site #973

Hong Kong, Hong Kong

Location

Unita Operativa di Ematologia con Trapianto, Site #529

Bari, 70124, Italy

Location

Istituto di Ematologia "L. & A. Seragnoli", Site #959

Bologna, 40138, Italy

Location

A.O. Universitaria Policlinico Vittorio Emanuele di Catania, Site #530

Catania, 95124, Italy

Location

Clinica Ematologica, Site #528

Genova, 16132, Italy

Location

Ospedale Niguarda Ca' Granda di Milano, Site #531

Milan, 20162, Italy

Location

S.C. Ematologia, Site #960

Modena, 41124, Italy

Location

San Gerardo Hospital, Site #961

Monza, 20900, Italy

Location

U.O.C Ematologia con trapianto di midollo osseo, Site #560

Napoli, 80131, Italy

Location

Universita Federico II, Site #510

Napoli, Italy

Location

SCDU Medicina Interna II - Indirizzo Ematologico, Site #785

Orbassano, 10043, Italy

Location

Dipartimento di Biotecnologie Cellulari ed Ematologia Universita La Sapienza - Policlinico Umberto I, Site #511

Rome, 00161, Italy

Location

U.O. di Ematologia - Ospedale S. Eugenio, Site #962

Rome, 144, Italy

Location

VU Medical Centre - Department Haematology, Site #948

Amsterdam, 1081-HV, Netherlands

Location

Auckland City Hospital, Site #921

Grafton, Auckland, 1023, New Zealand

Location

Christchurch Hospital, Site #922

Christchurch, New Zealand

Location

Waikato Hospital, Site #977

Hamilton, New Zealand

Location

North Shore Hospital, Site #976

Takapuna, 0740, New Zealand

Location

Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Medyczne, Site #548

Gdansk, Poland

Location

Malopolskie Centrum Medyczne, Site #546

Krakow, Poland

Location

Klinika Hematologii Wojewodzkiego Szpitala Specjalistycznego, Site #550

Lodz, Poland

Location

Oddzial Hematologii, Site #551

Rzeszów, 35-055, Poland

Location

Katedra i Klinika Hematologii, Site #547

Wroclaw, Poland

Location

Instituto Portugues de Oncologia, Site #545

Lisbon, 1099-023, Portugal

Location

Fundacion de Investigacion de Diego, Site #199

San Juan, 00927, Puerto Rico

Location

Singapore General Hospital, Site #939

Singapore, Singapore

Location

Narodny onkologicky ustav, Site #532

Bratislava, 833 10, Slovakia

Location

Univerzitna nemocnica Martin, Site #533

Martin, 036 59, Slovakia

Location

The Catholic University of Korea, Site #938

Seocho-gu, Seoul, 137-701, South Korea

Location

Complejo Hospitalario Universitario A Coruna, Hospital "Teresa Herrera," Site #554

A Coruña, 15006, Spain

Location

Hospital Universitari Germans Trias i Pujol, Site #512

Badalona, 08916, Spain

Location

Hospital Clinic, Site #963

Barcelona, 08036, Spain

Location

Institut Catala d' Oncologia de Girona, S. de Hematologia Clinica, Site #734

Girona, 17007, Spain

Location

Hospital Universitari Son Espases, Site #553

Islas Baleares, 07010, Spain

Location

Hospital Universitario La Princesa, Site #555

Madrid, 28006, Spain

Location

Hospital Gregorio Maranon, Site #536

Madrid, 28007, Spain

Location

H.U. Ramon y Cajal, Site #538

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre, Site #537

Madrid, 28041, Spain

Location

Hospital La Paz, Site #966

Madrid, 28046, Spain

Location

Hospital Universitario Central de Asturias, Site #535

Oviedo, 33006, Spain

Location

Hospital Universitario de Salamanca, Site #965

Salamanca, 37007, Spain

Location

Hospital Clinico Universitario de Valencia, Site #964

Valencia, 46010, Spain

Location

Skane University Hospital, Site #944

Lund, Sweden

Location

Karolinska University Hospital Huddinge, Site #534

Stockholm, Sweden

Location

Karolinska University Hospital Solna, Site #763

Stockholm, Sweden

Location

Uppsala University Hospital, Site #945

Uppsala, Sweden

Location

Kantonsspital Aarau, Site #541

Aarau, 5001, Switzerland

Location

Kantonsspital St. Gallen, Site #707

Sankt Gallen, 9007, Switzerland

Location

Kaohsiung Chang Gung Memorial Hospital, Site #980

Kaohsiung City, Taiwan

Location

China Medical University Hospital, Site #978

Taiching, 40447, Taiwan

Location

National Taiwan University Hospital, Site #979

Taipei, 10002, Taiwan

Location

Western General Hospital, Site #556

Edinburgh, EH4 2XU, United Kingdom

Location

Kent and Medway Cancer Research Network, Site #558

Gillingham, United Kingdom

Location

University of Glasgow, Site #797

Glasgow, G120SB, United Kingdom

Location

St. James University Hospital, Site #540

Leeds, LS9 7TF, United Kingdom

Location

Royal Liverpool University Hospital, Site #969

Liverpool, L7 8XP, United Kingdom

Location

Hammersmith Hospital, Site #967

London, United Kingdom

Location

Newcastle University, Site #970

Newcastle, United Kingdom

Location

Norfolk & Norwich University Hospital Foundation Trust, Site #557

Norwich, United Kingdom

Location

Nottingham University Hospitals NHS Trust, Site #968

Nottingham, NG5 1PB, United Kingdom

Location

Oxford University Hospitals NHS Trust, Site #543

Oxford, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 34699069 DERIVED

• 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.

  PMID: 27083332 DERIVED

MeSH Terms

Conditions

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

Interventions

ponatinib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

Trial was discontinued early.

Results Point of Contact

• Title: Maureen Conlan, Senior Medical Director
• Organization: ARIAD Pharmaceuticals, Inc.

Maureen.Conlan@ariad.com

1-617-621-2316

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 26, 2012
• Study Start: June 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 17, 2014
• Results First Posted: October 21, 2014

Record last verified: 2014-10

Locations

IT (12); HK (2); KR (1); GB (10); TW (3); US (67); CA (2); AU (6); PR (1); CH (2); CZ (4); PL (5); NL (1); BE (4); SG (1); SE (4); ES (13); FR (14); DE (9); SL (2); FI (1); NZ (4); PT (1)