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

• 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: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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.

Contacts and Locations

Locations

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

• 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

More Information

Additional Information:

Iclusig® (ponatinib) US Prescribing Information 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cortes 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.

• 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
• 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/

• 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:

Ponatinib; 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; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action