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Ponatinib in Participants With Resistant Chronic Phase Chronic Myeloid Leukemia (CP-CML) to Characterize the Efficacy and Safety of a Range of Doses (OPTIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02467270
Recruitment Status : Active, not recruiting
First Posted : June 10, 2015
Results First Posted : June 14, 2021
Last Update Posted : January 13, 2022
Sponsor:
Information provided by (Responsible Party):
Takeda

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.

Condition or disease Intervention/treatment Phase
Myeloid Leukemia, Chronic, Chronic Phase Drug: Ponatinib Phase 2

Detailed Description:

The drug being tested in this study is ponatinib. This study will characterize the safety and efficacy of ponatinib over a range of 3 starting doses.

The study will enroll 276 participants in 3 cohorts and each cohort will have 92 participants. All the participants will be randomized to receive once-daily oral administration of 1 of 3 starting doses of ponatinib:

  • Cohort A: 45 mg ponatinib tablet
  • Cohort B: 30 mg ponatinib tablet
  • Cohort C: 15 mg ponatinib tablet

The study is designed to consist of 2 periods: 24-cycle Main treatment period and optional treatment continuation period. Participants will be treated with their randomized dose of study drug in the Main Treatment Period until the occurrence of at least one of the following: absence of CHR by 3 months, absence of MCyR at 12 months, absence of <=1% BCR-ABL1IS at 12 months, loss of <=1% BCR-ABL1IS development of intolerance, or completion of all 24 cycles of treatment (whichever occurs first). Following completion of approximately 5 years or following early withdrawal, participants may enter into an optional treatment continuation period.

This multi-center trial will be conducted in the United States, United Kingdom, Republic of Korea, Spain, France, Taiwan, Australia, Canada, Italy, Chile, Japan, Germany, Argentina, Poland, Czech Republic, Denmark, Hong Kong, Portugal, Russia, Singapore, Switzerland, and Sweden. The overall time to participate in this study is approximately 96 months. Participants will make a final visit to the clinic approximately 30 days after the last dose of study treatment.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 283 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 30, 2015
Actual Primary Completion Date : April 14, 2020
Estimated Study Completion Date : June 1, 2024


Arm Intervention/treatment
Experimental: Cohort A: Ponatinib 45 mg
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Drug: Ponatinib
Tablet, taken orally once daily.
Other Names:
  • Iclusig
  • AP24534

Experimental: Cohort B: Ponatinib 30 mg
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Drug: Ponatinib
Tablet, taken orally once daily.
Other Names:
  • Iclusig
  • AP24534

Experimental: Cohort C: Ponatinib 15 mg
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Drug: Ponatinib
Tablet, taken orally once daily.
Other Names:
  • Iclusig
  • AP24534




Primary Outcome Measures :
  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 [ Time Frame: 12 months after the first dose of study treatment ]
    MR2 is 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.


Secondary Outcome Measures :
  1. Percentage of Participants With Major Molecular Response (MMR/MR3) [ Time Frame: 12 months after the first dose of study treatment ]
    MMR/MR3 is defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL ≤0.1% on the international scale (equivalent to a 3-log reduction in transcript).

  2. Percentage of Participants With Major Cytogenetic Response (MCyR) [ Time Frame: 12 months after the first dose of study treatment ]
    MCyR is defined as percentage of participants with complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Cytogenetic response is the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow (BM). Response is further defined as MCyR: CCyR or PCyR, where CCyR: 0% Ph + metaphases; PCyR: >0 to 35% Ph + metaphases.

  3. Duration of Major Molecular Response (MMR/MR3) [ Time Frame: Baseline up to approximately 8 years ]
    Duration of MMR/MR3 is defined as the interval between the first assessment at which the criteria for <=0.1% MMR are met until the earliest date at which loss of <=0.1% MMR occurs, or the criteria for progression are met. Progression to accelerated phase (AP) is defined as: >= 15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets per liter (/L) in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to blast Phase (BP) is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

  4. 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) [ Time Frame: From first dose up to 30 days after last dose of the study drug up to data cut-off date: 31 May 2020 (Up to approximately 5 years) ]
    Percentage of participants with adjusted incidence rates who developed AOEs and VTEs were categorized according to arterial occlusive events and venous thrombotic events. AE is any untoward medical occurrence in participant administered medicinal investigational drug. Untoward medical occurrence does not necessarily have to have causal relationship with treatment. SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is congenital anomaly/birth defect/is medically important event that may not be immediately life-threatening/result in death or hospitalization, but may jeopardize participant/may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.

  5. Percentage of Participants With Complete Cytogenetic Response (CCyR) [ Time Frame: Month 12 ]
    Cytogenetic response is defined as the percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. CCyR is defined as 0% Ph+ metaphases.

  6. Percentage of Participants With Molecular Response 4 (MR4) and Molecular Response (MR4.5) [ Time Frame: Up to approximately 8 years ]
    MR4 is defined as <=0.01% BCR-ABL1IS. MR 4.5 is defined as <=0.0032% BCR-ALB1IS.

  7. Percentage of Participants With Molecular Response 1 (MR1) [ Time Frame: 3 months after the first dose of study treatment ]
    MR1 is defined as percentage of participants achieving a ratio of <=10% Breakpoint Cluster Region-abelson (BCR-ABL1) transcripts on the international scale. MR1 is molecular response with 1-log reduction in transcript.

  8. Percentage of Participants With Complete Hematologic Response (CHR) [ Time Frame: 3 months after the first dose of study treatment ]
    CHR is defined as achieving all of the following measurements: white blood cells (WBC) <= institutional upper limit of normal (ULN), platelets <450,000 per cubic millimeter (/mm^3), no blasts or promyelocytes in peripheral blood, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%, and no extramedullary involvement (including no hepatomegaly or splenomegaly).

  9. Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption [ Time Frame: Up to data cut-off: 31 May 2020 (Approximately 5 years) ]
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

  10. Kaplan-Meier Estimate of Duration of Response (DOR) of <=1% BCR-ABL1 IS (MR2) at Months 12 and 24 [ Time Frame: 12 and 24 months after the first dose of study treatment ]
    DOR (≤1% BCR-ABL1IS) is defined as interval between first assessment at which criteria for ≤1% BCR-ABL1IS are met until earliest date at which loss of ≤1% BCR-ABL1IS occurs, or criteria for progression accelerated phase (AP) or blast Phase (BP) of chronic myeloid leukemia (CML) are met. Loss of ≤1% BCR-ABL1IS is an increase to >1% of BCR-ABL1IS. Progression to AP: ≥15% and <30% blasts in peripheral blood or bone marrow or ≥20% basophils in peripheral blood or bone marrow or ≥30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets per liter in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP: ≥30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. Kaplan-Meier method was used for analysis of percentage of participants who achieved DOR of 12 and 24 months.

  11. Kaplan-Meier Estimate of Duration of Response (DOR) of Major Molecular Response (MMR/MR3) [ Time Frame: 12 and 24 months after the first dose of study treatment ]
    Duration of MMR/MR3 is defined as interval between first assessment at which criteria for MMR are met until earliest date at which loss of MMR occurs, or criteria for progression (progression to AP or BP of CML) are met. Participants remaining in MMR will be censored at last date at which criteria for MMR are met. Loss of MMR is an increase to >0.1% of BCR-ABL1IS. Progression to AP: >= 15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts+promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. Kaplan-Meier method was used for analysis of percentage of participants who achieved DOR of 12 and 24 months.

  12. Duration of Response in Responders [ Time Frame: Baseline up to data cut-off: 31 May 2020 (Approximately 5 years) ]
    Duration of response in "responders" is defined as any participants who achieved ≤1% BCR-ABL1IS at any time during the study. Responders are defined as those participants who meet all of the following: are randomized and treated, respond at 12 months after the initiation of study treatment, and undergo baseline polymerase chain reaction (PCR) assessment.

  13. Time to Response [ Time Frame: Baseline up to data cut-off: 31 May 2020 (Approximately 5 years) ]
    Time to response was defined as the time interval from the date of the first dose of the study drug until the initial observation of CR or PR for participants with confirmed CR/PR. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the Baseline sum diameters.

  14. Percentage of Participants With Progression to Accelerated Phase (AP)-Chronic Myeloid Leukemia (CML) or Blast Phase (BP)-CML [ Time Frame: From first dose date of study treatment up to data cut-off: 31 May 2020 (Approximately 5 years) ]
    Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

  15. Progression-free Survival (PFS) [ Time Frame: Up to data cut-off: 31 May 2020 (Up to approximately 5 years) ]
    PFS is defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression are met (progression to the AP or BP of CML), or death due to any cause, censored at the last response assessment. Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

  16. Overall Survival (OS) [ Time Frame: Up to data cut-off: 31 May 2020 (Up to approximately 5 years) ]
    OS is defined as the interval between the first does of study treatment and death due to any cause, censored at the last contact date when the participant was alive.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.

    i Variant translocations are only allowed provided they meet inclusion criterion 1d.

    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

  2. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  3. 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)

  4. 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

  5. Have normal pancreatic status as defined by the following criterion:

    o] Serum lipase and amylase <=1.5*ULN

  6. 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.
  7. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
  8. 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).
  9. Provide written informed consent.
  10. Be willing and able to comply with scheduled visits and study procedures.
  11. Have recovered from toxicities related to prior anticancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 grade <=1.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. 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).
  5. Are taking medications with a known risk of Torsades de Pointes.
  6. Have previously been treated with ponatinib.
  7. Have active CNS disease as evidenced by cytology or pathology; in the absence of clinical CNS disease, lumbar puncture is not required. History itself of CNS involvement is not exclusionary if CNS has been cleared with a documented negative lumbar puncture.
  8. 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

  9. 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.
  10. Have poorly controlled diabetes defined as HbA1c values of >7.5%. Participants with preexisting, well-controlled diabetes are not excluded.
  11. Have a significant bleeding disorder unrelated to CML.
  12. Have a history of alcohol abuse.
  13. Have a history of either acute pancreatitis within 1 year of study enrollment or of chronic pancreatitis.
  14. Have malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drug.
  15. 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.
  16. Are pregnant or lactating.
  17. Have undergone major surgery (with the exception of minor surgical procedures, such as catheter placement or BM biopsy) within 14 days prior to first dose of ponatinib.
  18. Have an active infection which requires intravenous antibiotics.
  19. Have a known history of human immunodeficiency virus infection; testing is not required in the absence of prior documentation or known history.
  20. Have any condition or illness that, in the opinion of the investigator, would compromise participant safety or interfere with the evaluation of the drug.
  21. Have hypersensitivity to the ponatinib active substance or to any of its inactive ingredients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02467270


Locations
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Layout table for location information
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Indiana
Indiana Blood & Marrow Transplantation
Indianapolis, Indiana, United States, 46237
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Michigan
Michigan Medicine
Ann Arbor, Michigan, United States, 48109
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota Medical School
Minneapolis, Minnesota, United States, 55455
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan-Kettering Cancer Center - New York
New York, New York, United States, 10065
NewYork-Presbyterian Weill Cornell Medical Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Taussig Cancer Institute Main Campus
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Argentina
Fundaleu
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1114AAN
Hospital General de Agudo Jose Maria Ramos Mejia
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1221ADC
Hospital Italiano La Plata
La Plata, Buenos Aires, Argentina, B1900AXI
Australia, New South Wales
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia, 2065
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Canada, Ontario
Princess Margaret Hospital - Toronto
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Canada, Saskatchewan
Saskatchewan Cancer Agency
Regina, Saskatchewan, Canada, S4T 7T1
Chile
Hospital del Salvador
Providencia, Santiago, Chile, 7500922
Centro de Investigaciones Clinicas Vina del Mar
Vina del Mar, Valparaiso, Chile, 2540364
Czechia
Ustav Hematologie a Krevni Transfuze Praha
Prague, Praha, Czechia, 12820
Fakultni Nemocnice Olomouc
Olomouc, Czechia, 772 00
Denmark
Aarhus University Hospital
Aarhus C, \Aarhus, Denmark, DK-8000
France
Centre de Lutte Contre le Cancer - Institut Bergonie
Bordeaux, Aquitaine, France, 33076
Centre Hospitalier Universitaire de Nancy Hopital de Brabois
Vandoeuvre les Nancy, Lorraine, France, 54511
Institut Universitaire du Cancer de Toulouse Oncopole
Toulouse Cedex 9, Midi-pyrenees, France, 31059
Centre Hospitalier Regional Universitaire de Lille
Lille cedex, NORD Pas-de-calais, France, 59037
Center Hospitalier Universitaire d'Angers
Angers Cedex 9, PAYS DE LA Loire, France, 49933
Centre Hospitalier Universitaire de Nantes Hotel Dieu
Nantes Cedex 1, PAYS DE LA Loire, France, 44093
Centre Hospitalier Universitaire de Poitiers
Poitiers Cedex, Poitou-charentes, France, 86021
Centre Hospitalier Universitaire de Nice Hopital l'Archet
Nice Cedex 3, Provence Alpes COTE D'azur, France, 06202
Germany
Universitaetsklinikum Heidelberg
Mannheim, Baden-wuerttemberg, Germany, 68169
Universitatsklinikum Ulm
Ulm, Baden-wuerttemberg, Germany, 89081
Universitatsmedizin Rostock
Rostock, Mecklenburg-vorpommern, Germany, 18057
Uniklinik RWTH Aachen
Aachen, Nordrhein-westfalen, Germany, 52074
Universitaetsklinikum Essen
Essen, Nordrhein-westfalen, Germany, 45147
Universitatsklinikum Jena
Jena, Thuringen, Germany, 07747
Charite Universitatsmedizin Berlin
Berlin, Germany, 13353
Universitatsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong, 852
Italy
Azienda Ospedaliera San Gerardo di Monza
Monza, Monza E Brianza, Italy, 20090
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Pesaro, Pesaro E Urbino, Italy, 61100
Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
Catania, Italy, 95124
Azienda Ospedaliera Universitaria San Martino
Genova, Italy, 16132
Azienda Sanitaria Locale di Pescara Ospedale Civile Dello Spirito Santo
Pescara, Italy, 65124
Sapienza Universita Di Roma
Roma, Italy, 00161
AOUI - Ospedale Policlinico "Giambattista Rossi" di Borgo Roma
Verona, Italy, 37134
Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, Korea, Republic of, 6591
Poland
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
Wroclaw, Dolnoslaskie, Poland, 50-367
Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Lodz, Lodzkie, Poland, 93-510
Malopolskie Centrum Medyczne
Krakow, Malopolskie, Poland, 30-510
Instytut Hematologii i Transfuzjologii
Warszawa, Mazowieckie, Poland, 02-776
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomorskie, Poland, 80-952
Portugal
Instituto Portugues de Oncologia de Lisboa Francisco Gentil
Lisboa, Portugal, 1090-023
Centro Hospitalar Sao Joao
Porto, Portugal, 4200-319
Russian Federation
Rostov State Medical University
Rostov-na-Donu, Rostov, Russian Federation, 344022
Chelyabinsk Regional Clinical Hospital
Chelyabinsk, Russian Federation, 454076
Kemerovo Regional Clinical Hospital
Kemerovo, Russian Federation, 650066
GBUZ Moscow Clinical Scientific Center DZM
Moscow, Russian Federation, 111123
Russian Academy of Medical Science
Moscow, Russian Federation, 125167
FGU Russian Scientific Research Institute of Hematology and Transfusiology
Saint Petersburg, Russian Federation, 191024
Almazov Federal North-West Medical Research Centre of Department of Health of Russian Federation
Saint Petersburg, Russian Federation, 197341
Samara State Medical University
Samara, Russian Federation, 443099
Saratov State Medical University
Saratov, Russian Federation, 355018
Singapore
Singapore General Hospital
Singapore, Singapore, 169856
Spain
Hospital Regional Universitario Carlos Haya
Malaga, Andalucia, Spain, 29010
Hospital Universitario de Gran Canaria Doctor Nergrin
Las Palmas de Gran Canaria, LAS Palmas, Spain, 35010
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Hospital Universitario de La Princesa
Madrid, Spain, 28006
Hospital Universitario Ramon Y Cajal
Madrid, Spain, 28034
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Sweden
Akademiska Sjukhuset
Uppsala, Sweden, 751 85
Switzerland
University Hospital Zurich
Zurich, Switzerland, 8091
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
United Kingdom
Royal Liverpool University Hospital NHS Trust
Liverpool, England, United Kingdom, L7 8XP
King's College Hospital NHS Foundation Trust
London, England, United Kingdom, SE5 9RS
Imperial College Healthcare NHS Trust
London, England, United Kingdom, W12 0NN
Nottingham City Hospital NHS Trust
Nottingham, England, United Kingdom, NG5 1PB
Churchill Hospital
Oxford, England, United Kingdom, OX3 7LE
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G12 0YN
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Study Director Clinical Science Takeda
  Study Documents (Full-Text)

Documents provided by Takeda:
Study Protocol  [PDF] October 5, 2020
Statistical Analysis Plan  [PDF] December 17, 2019

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02467270    
Other Study ID Numbers: AP24534-14-203
2014-001617-12 ( EudraCT Number )
15/LO/1192 ( Registry Identifier: NRES )
U1111-1238-0007 ( Other Grant/Funding Number: WHO )
First Posted: June 10, 2015    Key Record Dates
Results First Posted: June 14, 2021
Last Update Posted: January 13, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
Chronic Phase Chronic Myeloid Leukemia
Molecular Response
CML
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
CP-CML
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Ponatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action