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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02467270




Registration number
NCT02467270
Ethics application status
Date submitted
2/06/2015
Date registered
10/06/2015

Titles & IDs
Public title
Ponatinib in Participants With Resistant Chronic Phase Chronic Myeloid Leukemia (CP-CML) to Characterize the Efficacy and Safety of a Range of Doses
Scientific 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
Secondary ID [1] 0 0
2014-001617-12
Secondary ID [2] 0 0
AP24534-14-203
Universal Trial Number (UTN)
Trial acronym
OPTIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myeloid Leukemia, Chronic, Chronic Phase 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ponatinib

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.

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.

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.


Treatment: Drugs: Ponatinib
Tablet, taken orally once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
12 months after the first dose of study treatment
Secondary outcome [1] 0 0
Percentage of Participants With Major Molecular Response (MMR/MR3)
Timepoint [1] 0 0
12 months after the first dose of study treatment
Secondary outcome [2] 0 0
Percentage of Participants With Major Cytogenetic Response (MCyR)
Timepoint [2] 0 0
12 months after the first dose of study treatment
Secondary outcome [3] 0 0
Duration of Major Molecular Response (MMR/MR3)
Timepoint [3] 0 0
Baseline up to approximately 8 years
Secondary outcome [4] 0 0
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)
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Percentage of Participants With Complete Cytogenetic Response (CCyR)
Timepoint [5] 0 0
Month 12
Secondary outcome [6] 0 0
Percentage of Participants With Molecular Response 4 (MR4) and Molecular Response (MR4.5)
Timepoint [6] 0 0
Up to approximately 8 years
Secondary outcome [7] 0 0
Percentage of Participants With Molecular Response 1 (MR1)
Timepoint [7] 0 0
3 months after the first dose of study treatment
Secondary outcome [8] 0 0
Percentage of Participants With Complete Hematologic Response (CHR)
Timepoint [8] 0 0
3 months after the first dose of study treatment
Secondary outcome [9] 0 0
Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
Timepoint [9] 0 0
Up to data cut-off: 31 May 2020 (Approximately 5 years)
Secondary outcome [10] 0 0
Kaplan-Meier Estimate of Duration of Response (DOR) of <=1% BCR-ABL1 IS (MR2) at Months 12 and 24
Timepoint [10] 0 0
12 and 24 months after the first dose of study treatment
Secondary outcome [11] 0 0
Kaplan-Meier Estimate of Duration of Response (DOR) of Major Molecular Response (MMR/MR3)
Timepoint [11] 0 0
12 and 24 months after the first dose of study treatment
Secondary outcome [12] 0 0
Duration of Response in Responders
Timepoint [12] 0 0
Baseline up to data cut-off: 31 May 2020 (Approximately 5 years)
Secondary outcome [13] 0 0
Time to Response
Timepoint [13] 0 0
Baseline up to data cut-off: 31 May 2020 (Approximately 5 years)
Secondary outcome [14] 0 0
Percentage of Participants With Progression to Accelerated Phase (AP)-Chronic Myeloid Leukemia (CML) or Blast Phase (BP)-CML
Timepoint [14] 0 0
From first dose date of study treatment up to data cut-off: 31 May 2020 (Approximately 5 years)
Secondary outcome [15] 0 0
Progression-free Survival (PFS)
Timepoint [15] 0 0
Up to data cut-off: 31 May 2020 (Up to approximately 5 years)
Secondary outcome [16] 0 0
Overall Survival (OS)
Timepoint [16] 0 0
Up to data cut-off: 31 May 2020 (Up to approximately 5 years)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
Accrual to date
Final
283
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Canada
State/province [18] 0 0
Saskatchewan
Country [19] 0 0
Chile
State/province [19] 0 0
Santiago
Country [20] 0 0
Chile
State/province [20] 0 0
Valparaiso
Country [21] 0 0
Czechia
State/province [21] 0 0
Praha
Country [22] 0 0
Czechia
State/province [22] 0 0
Olomouc
Country [23] 0 0
Denmark
State/province [23] 0 0
\Aarhus
Country [24] 0 0
France
State/province [24] 0 0
Aquitaine
Country [25] 0 0
France
State/province [25] 0 0
Lorraine
Country [26] 0 0
France
State/province [26] 0 0
Midi-pyrenees
Country [27] 0 0
France
State/province [27] 0 0
NORD Pas-de-calais
Country [28] 0 0
France
State/province [28] 0 0
PAYS DE LA Loire
Country [29] 0 0
France
State/province [29] 0 0
Poitou-charentes
Country [30] 0 0
France
State/province [30] 0 0
Provence Alpes COTE D'azur
Country [31] 0 0
Germany
State/province [31] 0 0
Baden-wuerttemberg
Country [32] 0 0
Germany
State/province [32] 0 0
Mecklenburg-vorpommern
Country [33] 0 0
Germany
State/province [33] 0 0
Nordrhein-westfalen
Country [34] 0 0
Germany
State/province [34] 0 0
Thuringen
Country [35] 0 0
Germany
State/province [35] 0 0
Berlin
Country [36] 0 0
Germany
State/province [36] 0 0
Hamburg
Country [37] 0 0
Hong Kong
State/province [37] 0 0
Hong Kong
Country [38] 0 0
Italy
State/province [38] 0 0
Monza E Brianza
Country [39] 0 0
Italy
State/province [39] 0 0
Pesaro E Urbino
Country [40] 0 0
Italy
State/province [40] 0 0
Catania
Country [41] 0 0
Italy
State/province [41] 0 0
Genova
Country [42] 0 0
Italy
State/province [42] 0 0
Pescara
Country [43] 0 0
Italy
State/province [43] 0 0
Roma
Country [44] 0 0
Italy
State/province [44] 0 0
Verona
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Korea, Republic of
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Seoul
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Poland
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Dolnoslaskie
Country [47] 0 0
Poland
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Lodzkie
Country [48] 0 0
Poland
State/province [48] 0 0
Malopolskie
Country [49] 0 0
Poland
State/province [49] 0 0
Mazowieckie
Country [50] 0 0
Poland
State/province [50] 0 0
Pomorskie
Country [51] 0 0
Portugal
State/province [51] 0 0
Lisboa
Country [52] 0 0
Portugal
State/province [52] 0 0
Porto
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Rostov
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Chelyabinsk
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Kemerovo
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Moscow
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Saint Petersburg
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Samara
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Saratov
Country [60] 0 0
Singapore
State/province [60] 0 0
Singapore
Country [61] 0 0
Spain
State/province [61] 0 0
Andalucia
Country [62] 0 0
Spain
State/province [62] 0 0
LAS Palmas
Country [63] 0 0
Spain
State/province [63] 0 0
Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Madrid
Country [65] 0 0
Spain
State/province [65] 0 0
Valencia
Country [66] 0 0
Sweden
State/province [66] 0 0
Uppsala
Country [67] 0 0
Switzerland
State/province [67] 0 0
Zurich
Country [68] 0 0
Taiwan
State/province [68] 0 0
Taipei
Country [69] 0 0
United Kingdom
State/province [69] 0 0
England
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Scotland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director Clinical Science
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02467270