Ponatinib in Participants With Resistant Chronic Phase Chronic Myeloid Leukemia (CP-CML) to Characterize the Efficacy and Safety of a Range of Doses
OPTIC
A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients With Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses
5 other identifiers
interventional
283
21 countries
86
Brief Summary
The purpose of this study is to characterize the efficacy of ponatinib administered in 3 starting doses (45 mg, 30 mg, and 15 mg daily) in participants with CP-CML who are resistant to prior tyrosine-kinase inhibitor (TKI) therapy or have T315I mutation, as measured by \<=1 % Breakpoint Cluster Region-Abelson Transcript Level using International Scale (BCR-ABL1IS) at 12 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2015
Longer than P75 for phase_2
86 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 2, 2015
CompletedFirst Posted
Study publicly available on registry
June 10, 2015
CompletedStudy Start
First participant enrolled
July 13, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 29, 2020
CompletedResults Posted
Study results publicly available
June 14, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 23, 2025
CompletedMarch 17, 2026
March 1, 2026
4.8 years
June 2, 2015
April 14, 2021
March 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Molecular Response (MR2: <=1% Breakpoint Cluster Region-Abelson Transcript Level) as Measured by the International Scale (BCR-ABL1IS) at Month 12
MR2 was defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL \<=1% Breakpoint Cluster Region-Abelson Transcript Level as measured by the International Scale (BCR-ABL1IS), equivalent to a 2-log reduction in transcript.
12 months after the first dose of study treatment
Secondary Outcomes (16)
Percentage of Participants With Major Molecular Response (MMR/MR3)
12, 24 and 60 months after the first dose of study treatment
Percentage of Participants With Major Cytogenetic Response (MCyR)
12 months after the first dose of study treatment
Duration of Major Molecular Response (MMR/MR3)
Baseline up to approximately 8.9 years
Percentage of Participants With Adjusted Incidence Rates for Treatment Emergent Arterial Occlusive Events (AOEs), Venous Thrombotic Events (VTEs), Adverse Events (AEs), and Serious AEs (SAEs)
From first dose up to 30 days after last dose of the study drug (up to approximately 9.8 years)
Percentage of Participants With Complete Cytogenetic Response (CCyR)
Month 12
- +11 more secondary outcomes
Study Arms (6)
Treatment Period: Cohort A: Ponatinib 45 milligrams (mg)
EXPERIMENTALParticipants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Treatment Period: Cohort B: Ponatinib 30 mg
EXPERIMENTALParticipants received ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Treatment Period: Cohort C: Ponatinib 15 mg
EXPERIMENTALParticipants received ponatinib 15 mg orally once daily in each 28 day Cycle.
Close-out Period: Cohort A: Ponatinib 45 mg
EXPERIMENTALParticipants received ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Close-out Period: Cohort B: Ponatinib 30 mg
EXPERIMENTALParticipants received ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Close-out Period: Cohort C: Ponatinib 15 mg
EXPERIMENTALParticipants received ponatinib 15 mg orally once daily in each 28 day Cycle.
Interventions
Tablet, taken orally once daily.
Eligibility Criteria
You may qualify if:
- Have chronic phase-chronic myelogenous leukemia/chronic myeloid leukemia (CP-CML) and have received at least two prior tyrosine kinase inhibitor (TKI) therapies and have demonstrated resistance to treatment OR have documented history of presence of T315I mutation after receiving any number of prior TKI.
- o\] The diagnosis of chronic myeloid leukemia (CML) will be made using standard hematopathologic and cytogenetic criteria; CP-CML will be defined by all of the following: i \<15% blasts in bone marrow ii \<30% blasts plus promyelocytes in bone marrow iii \<20% basophils in peripheral blood. iv \>= 100\*10\^9/liter (L) platelets (\>=100,000/mm\^3). v No evidence of extramedullary disease except hepatosplenomegaly vi No prior diagnosis of AP-CML, and BP-CML o\] Cytogenetic assessment at screening must demonstrate the BCR-ABL1 fusion by presence of the t(9;22) Philadelphia chromosome.
- o\] Resistance to prior TKI therapy is defined as follows (participants must meet at least 1 criterion): i Three months after the initiation of prior TKI therapy: No cytogenetic response (\>95% Ph+) or failure to achieve CHR or new mutation ii Six months after the initiation of prior TKI therapy: BCR-ABL1IS \>10% and/or Ph+ \>65% or new mutation iii Twelve months after the initiation of prior TKI therapy: BCR ABL1IS \>10% and/or Ph+ \>35% or new mutation iv At any time after the initiation of prior TKI therapy, the development of a new BCR-ABL1 kinase domain mutation(s) v At any time after the initiation of prior TKI therapy, the development of new clonal evolution vi At any time after the initiation of prior TKI therapy, the loss of CHR, or CCyR, or the confirmed loss of MMR in 2 consecutive tests, one of which has a BCR-ABL1IS transcript level of \>=1% or new mutation o\] \>1% of BCR-ABL1IS as shown by real-time polymerase chain reaction
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Have adequate renal function as defined by the following criterion:
- o\] Serum creatinine \<=1.5\*ULN for institution o\] Estimated creatinine clearance \>=30 milliliter per minute (mL/min) (Cockcroft-Gault formula)
- Have adequate hepatic function as defined by the following criteria:
- o\] Total serum bilirubin \<=1.5\*ULN, unless due to Gilbert's syndrome o\] Alanine transaminase (ALT) \<=2.5\*ULN, or \<=5\*ULN if leukemic infiltration of the liver is present o\] Aspartate transaminase (AST) \<=2.5\*ULN, or \<=5\*ULN if leukemic infiltration of the liver is present
- Have normal pancreatic status as defined by the following criterion:
- o\] Serum lipase and amylase \<=1.5\*ULN
- Have normal QT interval corrected (Frederica) (QTcF) interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of \<=450 milliseconds (ms) in males or \<=470 ms in females.
- Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
- Agree to use a highly effective form of contraception with sexual partners from randomization through at least 4 months after the end of treatment (for female and male participants who are fertile).
- Provide written informed consent.
- Be willing and able to comply with scheduled visits and study procedures.
- +1 more criteria
You may not qualify if:
- Have used any approved TKIs or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is longer, prior to receiving study drug.
- Received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib, or have not recovered (\>grade 1 by NCI CTCAE, version 4.0) from AEs (except alopecia), due to agents previously administered.
- Have undergone autologous or allogeneic stem cell transplant \<60 days prior to receiving the first dose of ponatinib; have any evidence of ongoing graft-versus-host disease (GVHD) or GVHD requiring immunosuppressive therapy.
- Are being considered for hematopoietic stem cell transplant (HSCT) within 6-12 months of enrollment (note: ponatinib is not to be used as a bridge to HSCT in this trial).
- Are taking medications with a known risk of Torsades de Pointes.
- Have previously been treated with ponatinib.
- Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- o\] Any history of myocardial infarction (MI), unstable angina, cerebrovascular accident, or Transient Ischemic Attack (TIA) o\] Any history of peripheral vascular infarction, including visceral infarction o\] Any revascularization procedure, including the placement of a stent o\] Congestive heart failure (CHF) (New York Heart Association \[NYHA\] class III or IV) within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal, per local institutional standards, within 6 months prior to enrollment o\] History of clinically significant (as determined by the treating physician) atrial arrhythmia or any history of ventricular arrhythmia o\] Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrollment
- Have uncontrolled hypertension (that is, \>150 and \>90 for systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively). Participants with hypertension should be under treatment at study entry to ensure blood pressure control. Those requiring 3 or more antihypertensive medications should be discussed with the medical monitor.
- Have poorly controlled diabetes defined as HbA1c values of \>7.5%. Participants with preexisting, well-controlled diabetes are not excluded.
- Have a significant bleeding disorder unrelated to CML.
- Have a history of alcohol abuse.
- Have a history of either acute pancreatitis within 1 year of study enrollment or of chronic pancreatitis.
- Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug.
- Have a history of another malignancy, other than cervical cancer in situ or basal cell or squamous cell carcinoma of the skin; the exception is if participants have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (86)
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Indiana Blood & Marrow Transplantation
Indianapolis, Indiana, 46237, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Michigan Medicine
Ann Arbor, Michigan, 48109, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
University of Minnesota Medical School
Minneapolis, Minnesota, 55455, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Memorial Sloan-Kettering Cancer Center - New York
New York, New York, 10065, United States
NewYork-Presbyterian Weill Cornell Medical Center
New York, New York, 10065, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cleveland Clinic Taussig Cancer Institute Main Campus
Cleveland, Ohio, 44195, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Fundaleu
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1114AAN, Argentina
Hospital General de Agudo Jose Maria Ramos Mejia
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1221ADC, Argentina
Hospital Italiano La Plata
La Plata, Buenos Aires, B1900AXI, Argentina
Royal North Shore Hospital
Saint Leonards, New South Wales, 2065, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Princess Margaret Hospital - Toronto
Toronto, Ontario, M5G 2M9, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Saskatchewan Cancer Agency
Regina, Saskatchewan, S4T 7T1, Canada
Centro de Investigaciones Clinicas Vina del Mar
Viña del Mar, Región de Valparaíso, 2540364, Chile
Hospital del Salvador
Providencia, Santiago Metropolitan, 7500922, Chile
Ustav Hematologie a Krevni Transfuze Praha
Prague, Prague, 12820, Czechia
Fakultni Nemocnice Olomouc
Olomouc, 772 00, Czechia
Aarhus University Hospital
Aarhus C, \Aarhus, DK-8000, Denmark
Centre de Lutte Contre le Cancer - Institut Bergonie
Bordeaux, Aquitaine, 33076, France
Centre Hospitalier Regional Universitaire de Lille
Lille, Hauts-de-France, 59037, France
Centre Hospitalier Universitaire de Nancy Hopital de Brabois
Vandœuvre-lès-Nancy, Lorraine, 54511, France
Institut Universitaire du Cancer de Toulouse Oncopole
Toulouse, Midi-pyrenees, 31059, France
Center Hospitalier Universitaire d'Angers
Angers, Pays de la Loire Region, 49933, France
Centre Hospitalier Universitaire de Nantes Hotel Dieu
Nantes, Pays de la Loire Region, 44093, France
Centre Hospitalier Universitaire de Poitiers
Poitiers, Poitou-charentes, 86021, France
Centre Hospitalier Universitaire de Nice Hopital l'Archet
Nice, Provence-Alpes-Côte d'Azur Region, 06202, France
Universitaetsklinikum Heidelberg
Mannheim, Baden-Wurttemberg, 68169, Germany
Universitatsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081, Germany
Universitatsmedizin Rostock
Rostock, Mecklenburg-Vorpommern, 18057, Germany
Uniklinik RWTH Aachen
Aachen, North Rhine-Westphalia, 52074, Germany
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45147, Germany
Universitatsklinikum Jena
Jena, Thuringia, 07747, Germany
Charite Universitatsmedizin Berlin
Berlin, 13353, Germany
Universitatsklinikum Hamburg-Eppendorf
Hamburg, 20246, Germany
Queen Mary Hospital
Hong Kong, 852, Hong Kong
Azienda Ospedaliera San Gerardo di Monza
Monza, Monza E Brianza, 20090, Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Pesaro, Pesaro E Urbino, 61100, Italy
Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
Catania, 95124, Italy
Azienda Ospedaliera Universitaria San Martino
Genova, 16132, Italy
Azienda Sanitaria Locale di Pescara Ospedale Civile Dello Spirito Santo
Pescara, 65124, Italy
Sapienza Universita Di Roma
Roma, 00161, Italy
AOUI - Ospedale Policlinico "Giambattista Rossi" di Borgo Roma
Verona, 37134, Italy
Malopolskie Centrum Medyczne
Krakow, Lesser Poland Voivodeship, 30-510, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
Wroclaw, Lower Silesian Voivodeship, 50-367, Poland
Instytut Hematologii i Transfuzjologii
Warsaw, Masovian Voivodeship, 02-776, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, 80-952, Poland
Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Lodz, Łódź Voivodeship, 93-510, Poland
Instituto Portugues de Oncologia de Lisboa Francisco Gentil
Lisbon, 1090-023, Portugal
Centro Hospitalar Sao Joao
Porto, 4200-319, Portugal
Rostov State Medical University
Rostov-on-Don, Rostov Oblast, 344022, Russia
Chelyabinsk Regional Clinical Hospital
Chelyabinsk, 454076, Russia
Kemerovo Regional Clinical Hospital
Kemerovo, 650066, Russia
GBUZ Moscow Clinical Scientific Center DZM
Moscow, 111123, Russia
Russian Academy of Medical Science
Moscow, 125167, Russia
FGU Russian Scientific Research Institute of Hematology and Transfusiology
Saint Petersburg, 191024, Russia
Almazov Federal North-West Medical Research Centre of Department of Health of Russian Federation
Saint Petersburg, 197341, Russia
Samara State Medical University
Samara, 443099, Russia
Saratov State Medical University
Saratov, 355018, Russia
Singapore General Hospital
Singapore, 169856, Singapore
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 6591, South Korea
Hospital Regional Universitario Carlos Haya
Málaga, Andalusia, 29010, Spain
Hospital Universitario de Gran Canaria Doctor Nergrin
Las Palmas de Gran Canaria, LAS Palmas, 35010, Spain
Hospital Clinic i Provincial de Barcelona
Barcelona, 08036, Spain
Hospital Universitario de La Princesa
Madrid, 28006, Spain
Hospital Universitario Ramon Y Cajal
Madrid, 28034, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Akademiska Sjukhuset
Uppsala, 751 85, Sweden
University Hospital Zurich
Zurich, 8091, Switzerland
National Taiwan University Hospital
Taipei, 100, Taiwan
Royal Liverpool University Hospital NHS Trust
Liverpool, England, L7 8XP, United Kingdom
King's College Hospital NHS Foundation Trust
London, England, SE5 9RS, United Kingdom
Imperial College Healthcare NHS Trust
London, England, W12 0NN, United Kingdom
Nottingham City Hospital NHS Trust
Nottingham, England, NG5 1PB, United Kingdom
Churchill Hospital
Oxford, England, OX3 7LE, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, G12 0YN, United Kingdom
Related Publications (2)
Kantarjian HM, Jabbour E, Deininger M, Abruzzese E, Apperley J, Cortes J, Chuah C, DeAngelo DJ, DiPersio J, Hochhaus A, Lipton J, Nicolini FE, Pinilla-Ibarz J, Rea D, Rosti G, Rousselot P, Shah NP, Talpaz M, Srivastava S, Ren X, Mauro M. Ponatinib after failure of second-generation tyrosine kinase inhibitor in resistant chronic-phase chronic myeloid leukemia. Am J Hematol. 2022 Nov;97(11):1419-1426. doi: 10.1002/ajh.26686. Epub 2022 Aug 30.
PMID: 36054756DERIVEDCortes J, Apperley J, Lomaia E, Moiraghi B, Undurraga Sutton M, Pavlovsky C, Chuah C, Sacha T, Lipton JH, Schiffer CA, McCloskey J, Hochhaus A, Rousselot P, Rosti G, de Lavallade H, Turkina A, Rojas C, Arthur CK, Maness L, Talpaz M, Mauro M, Hall T, Lu V, Srivastava S, Deininger M. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial. Blood. 2021 Nov 25;138(21):2042-2050. doi: 10.1182/blood.2021012082.
PMID: 34407543DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 2, 2015
First Posted
June 10, 2015
Study Start
July 13, 2015
Primary Completion
April 29, 2020
Study Completion
April 23, 2025
Last Updated
March 17, 2026
Results First Posted
June 14, 2021
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Access Criteria
- IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.