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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03589326




Registration number
NCT03589326
Ethics application status
Date submitted
5/07/2018
Date registered
17/07/2018

Titles & IDs
Public title
A Study of Ponatinib Versus Imatinib in Adults With Acute Lymphoblastic Leukemia
Scientific title
A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Secondary ID [1] 0 0
2018-000397-30
Secondary ID [2] 0 0
Ponatinib-3001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ALL) 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
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ponatinib
Treatment: Drugs - Imatinib
Treatment: Drugs - Vincristine
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Cytarabine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Prednisone

Experimental: Cohort A: Ponatinib 30 milligram (mg) - Ponatinib 30 mg, tablets, orally, once daily (QD), with vincristine 1.4 mg/m\^2 (max 2 mg) intravenous (IV), on Days 1 and 14 and dexamethasone 40 mg (\<60 years \[yrs\]) and 20 mg (=60 yrs), orally, once on Days 1 to 4, Days 11 to 14 for up to 3 cycles (each cycle=28 days) in induction phase (reduced dose of ponatinib 15 mg upon achievement of MRD-negative CR at end of induction) followed by ponatinib last induction phase dose with cytarabine, 1000 mg/m\^2 as 2-hour IV infusion (\<60 yrs) and 250 mg/m\^2 (=60 yrs) every 12 hours, IV on Days 1, 3, 5 of Cycles 2,4,6 and methotrexate, 1000 mg/m\^2 (\<60 yrs) and 250 mg/m\^2 (=60 yrs), IV infusion, on Day 1 of cycles 1, 3, 5 in consolidation phase followed by ponatinib last consolidation phase dose with vincristine 1.4 mg/m\^2 (max 2 mg), IV, on Day 1 and prednisone 200 mg (\<60 yrs), 100 mg (=60-69 yrs) and 50 mg(=70 yrs) on Days 1 to 5 for up to 11 cycles in maintenance phase up to data cut-off date: 12 August 2022.

Active comparator: Cohort B: Imatinib 600 mg - Imatinib 600 mg, tablets, orally, QD, with vincristine 1.4 mg/m\^2 (max 2 mg), IV, on Days 1 and 14 and dexamethasone 40 mg (\<60 yrs) and 20 mg (=60 yrs), orally, once on Days 1 to 4 and Days 11 to 14 in each 28-day cycle for up to 3 cycles in the induction phase followed by imatinib 600 mg, tablets, orally, QD, with cytarabine, 1000 mg/m\^2 every 12 hours as a 2-hour-IV infusion (\<60 yrs) and 250 mg/m\^2 every 12 hours (=60 yrs), IV on Days 1, 3, and 5 of each 28-day even cycles (Cycles 2, 4, and 6), and methotrexate, 1000 mg/m\^2 (\<60 yrs) and 250 mg/m\^2 (=60 yrs), IV infusion, on Day 1 of each 28-day odd cycles (Cycle 1, 3, and 5) in consolidation phase followed by imatinib 600 mg, tablets, orally, QD, along with vincristine 1.4 mg/m\^2 (max 2 mg), IV, on Day 1 and prednisone 200 mg (\<60 yrs), 100 mg (=60-69 yrs) and 50 mg (=70 yrs) on Days 1 through 5 in each 28-day cycle up to 11 cycles in maintenance phase up to data cut-off date: 12 August 2022.


Treatment: Drugs: Ponatinib
Ponatinib Tablets.

Treatment: Drugs: Imatinib
Imatinib Tablets.

Treatment: Drugs: Vincristine
Vincristine IV injection.

Treatment: Drugs: Dexamethasone
Dexamethasone Tablets.

Treatment: Drugs: Cytarabine
Cytarabine IV infusion.

Treatment: Drugs: Methotrexate
Methotrexate IV infusion.

Treatment: Drugs: Prednisone
Prednisone Tablets.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Minimal Residual Disease (MRD)-Negative Complete Remission (CR) at The End of Induction Phase
Timepoint [1] 0 0
From Cycle 1 through Cycle 3 (approximately 3 months) (Cycle length = 28 days)
Secondary outcome [1] 0 0
Event-free Survival (EFS)
Timepoint [1] 0 0
Baseline up to approximately 3 to 6 years
Secondary outcome [2] 0 0
Percentage of Participants With CR and Incomplete Complete Remission (CRi)
Timepoint [2] 0 0
End of Cycle 1 (approximately 1 month), Cycle 2 (approximately 2 months), Cycle 3 (approximately 3 months), and Cycle 9 (approximately 9 months) (Cycle length= 28 days)
Secondary outcome [3] 0 0
Percentage of Participants With Molecular Response
Timepoint [3] 0 0
End of Cycle 1 (approximately 1 month), Cycle 2 (approximately 2 months), Cycle 3 (approximately 3 months), and Cycle 9 (approximately 9 months) (Cycle length= 28 days)
Secondary outcome [4] 0 0
Percentage of Participants With Primary Induction Failure (PIF)
Timepoint [4] 0 0
Up to 3 months
Secondary outcome [5] 0 0
Percentage of Participants With Overall Response Rate (ORR)
Timepoint [5] 0 0
Up to 3 months
Secondary outcome [6] 0 0
Percentage of MRD-Negative CR
Timepoint [6] 0 0
Up to approximately 3 to 6 years
Secondary outcome [7] 0 0
Duration of MRD-Negative CR
Timepoint [7] 0 0
Up to approximately 3 to 6 years
Secondary outcome [8] 0 0
Duration of CR
Timepoint [8] 0 0
Up to approximately 3 to 6 years
Secondary outcome [9] 0 0
Time to Treatment Failure
Timepoint [9] 0 0
Up to approximately 6 years
Secondary outcome [10] 0 0
Duration of MR4.5
Timepoint [10] 0 0
Up to approximately 3 to 6 years
Secondary outcome [11] 0 0
Percentage of On-Study Participants With Overall Survival (OS)
Timepoint [11] 0 0
Up to approximately 3 to 6 years
Secondary outcome [12] 0 0
Percentage of On-Study Participants With Relapse From CR
Timepoint [12] 0 0
Up to approximately 3 to 6 years
Secondary outcome [13] 0 0
Overall Survival (OS)
Timepoint [13] 0 0
Up to approximately 3 to 6 years

Eligibility
Key inclusion criteria
1. Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2017 national comprehensive cancer network (NCCN) guidelines.
2. Eastern Cooperative Oncology Group (ECOG) performance status of <=2.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. With a history or current diagnosis of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML).
2. Prior/current treatment with any systemic anticancer therapy (including but not limited to any tyrosine kinase inhibitor [TKI]) and/or radiotherapy for ALL, with the exception of an optional prephase therapy or chemotherapy induction (no more than 1 cycle), which should be discussed with the sponsor's medical monitor/designee.
3. Currently taking drugs that are known to have a risk of causing prolonged corrected QT (QTc) or torsades de pointes (TdP) (unless these can be changed to acceptable alternatives or discontinued).
4. Taking any medications or herbal supplements that are known to be strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4 within at least 14 days before the first dose of study drug.
5. Uncontrolled active serious infection that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
6. Major surgery within 28 days before randomization (minor surgical procedures such as catheter placement or BM biopsy are not exclusionary criteria).
7. Known human immunodeficiency virus (HIV) seropositivity, known active hepatitis B or C infection.
8. History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis.
9. Uncontrolled hypertriglyceridemia (triglycerides >450 milligram per deciliter [mg/dL]).
10. Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
11. History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
12. Clinical manifestations of CNS or extramedullary involvement with ALL other than lymphadenopathy or hepatosplenomegaly.
13. Autoimmune disease with potential CNS involvement.
14. Known significant neuropathy of Grade >=2 severity.
15. Clinically significant, uncontrolled, or active cardiovascular, cerebrovascular, or peripheral vascular disease, or history of or active venous thrombotic/embolic event (VTE) disease.
16. Have a significant bleeding disorder unrelated to ALL.

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 3
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [2] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
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
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Argentina
State/province [11] 0 0
Cordoba
Country [12] 0 0
Austria
State/province [12] 0 0
Upper Austria
Country [13] 0 0
Austria
State/province [13] 0 0
Vienna
Country [14] 0 0
Brazil
State/province [14] 0 0
Bahia
Country [15] 0 0
Brazil
State/province [15] 0 0
Parana
Country [16] 0 0
Brazil
State/province [16] 0 0
RIO Grande DO SUL
Country [17] 0 0
Brazil
State/province [17] 0 0
SAO Paulo
Country [18] 0 0
Brazil
State/province [18] 0 0
Rio de Janeiro
Country [19] 0 0
Brazil
State/province [19] 0 0
Sao Paulo
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Sofiya
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
China
State/province [24] 0 0
Henan
Country [25] 0 0
China
State/province [25] 0 0
Jiangsu
Country [26] 0 0
China
State/province [26] 0 0
Jilin
Country [27] 0 0
China
State/province [27] 0 0
Zhejiang
Country [28] 0 0
China
State/province [28] 0 0
Tianjin
Country [29] 0 0
Finland
State/province [29] 0 0
Helsinki
Country [30] 0 0
France
State/province [30] 0 0
Ile-de-france
Country [31] 0 0
France
State/province [31] 0 0
Midi-pyrenees
Country [32] 0 0
France
State/province [32] 0 0
PAYS DE LA Loire
Country [33] 0 0
France
State/province [33] 0 0
Rhone-alpes
Country [34] 0 0
Greece
State/province [34] 0 0
Attica
Country [35] 0 0
Greece
State/province [35] 0 0
Peloponnese
Country [36] 0 0
Italy
State/province [36] 0 0
Forli-cesena
Country [37] 0 0
Italy
State/province [37] 0 0
Liguria
Country [38] 0 0
Italy
State/province [38] 0 0
Monza E Brianza
Country [39] 0 0
Italy
State/province [39] 0 0
Reggio Nella Emilia
Country [40] 0 0
Italy
State/province [40] 0 0
Venezia
Country [41] 0 0
Italy
State/province [41] 0 0
Bologna
Country [42] 0 0
Italy
State/province [42] 0 0
Lecce
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Modena
Country [45] 0 0
Italy
State/province [45] 0 0
Palermo
Country [46] 0 0
Italy
State/province [46] 0 0
Ravenna
Country [47] 0 0
Italy
State/province [47] 0 0
Roma
Country [48] 0 0
Japan
State/province [48] 0 0
Chiba
Country [49] 0 0
Japan
State/province [49] 0 0
Hokkaido
Country [50] 0 0
Japan
State/province [50] 0 0
Kanagawa
Country [51] 0 0
Japan
State/province [51] 0 0
Okayama
Country [52] 0 0
Japan
State/province [52] 0 0
Fukushima
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Gyeonggi-do
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Gyeongsangbuk-do
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Jeollabuk-do
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Busan
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Daegu
Country [58] 0 0
Mexico
State/province [58] 0 0
Nuevo LEON
Country [59] 0 0
Poland
State/province [59] 0 0
Dolnoslaskie
Country [60] 0 0
Poland
State/province [60] 0 0
Malopolskie
Country [61] 0 0
Poland
State/province [61] 0 0
Pomorskie
Country [62] 0 0
Poland
State/province [62] 0 0
Warminsko-mazurskie
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Moscow CITY
Country [64] 0 0
Russian Federation
State/province [64] 0 0
Sverdlovsk
Country [65] 0 0
Russian Federation
State/province [65] 0 0
Moscow
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Saint Petersburg
Country [67] 0 0
Spain
State/province [67] 0 0
Cataluna
Country [68] 0 0
Spain
State/province [68] 0 0
Barcelona
Country [69] 0 0
Spain
State/province [69] 0 0
Salamanca
Country [70] 0 0
Spain
State/province [70] 0 0
Valencia
Country [71] 0 0
Taiwan
State/province [71] 0 0
Hualien
Country [72] 0 0
Taiwan
State/province [72] 0 0
Taichung CITY
Country [73] 0 0
Taiwan
State/province [73] 0 0
Tainan CITY
Country [74] 0 0
Turkey
State/province [74] 0 0
Ankara

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
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.