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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01207440




Registration number
NCT01207440
Ethics application status
Date submitted
20/09/2010
Date registered
23/09/2010

Titles & IDs
Public title
Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)
Scientific title
A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia
Secondary ID [1] 0 0
2010-020414-28
Secondary ID [2] 0 0
AP24534-10-201
Universal Trial Number (UTN)
Trial acronym
PACE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia 0 0
Ph+ Acute Lymphoblastic Leukemia 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

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

Experimental: Cohort A: CP-CML R-I - CP-CML participants R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Experimental: Cohort B: CP-CML with T315I Mutation - CP-CML participants who had T315I mutation of breakpoint cluster region-Abelson complex (BCR-ABL) were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Experimental: Cohort C: Accelerated Phase (AP)-CML R-I - AP-CML R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Experimental: Cohort D: AP-CML with T315I Mutation - AP-CML participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Experimental: Cohort E: Blast Phase (BP)-CML/Ph+ ALL R-I - BP-CML or Ph+ ALL R-I to dasatinib or nilotinib or Ph+ ALL R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Experimental: Cohort F: BP-CML or Ph+ ALL with T315I Mutation - BP-CML or Ph+ ALL participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Experimental: Unassigned to Cohorts A-F - Participants who were not assigned to any of the cohorts and have no T315I mutation at study entry and were not R-I to dasatinib or nilotinib, administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).


Treatment: Drugs: Ponatinib
Ponatinib tablets.

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

Outcomes
Primary outcome [1] 0 0
Percentage of CP-CML Participants With Major Cytogenetic Response (MCyR)
Timepoint [1] 0 0
Up to 12 months after initiation of study treatment
Primary outcome [2] 0 0
Percentage of AP-CML Participants With Major Hematologic Response (MaHR)
Timepoint [2] 0 0
Up to 6 months after initiation of study treatment
Primary outcome [3] 0 0
Percentage of BP-CML/Ph+ ALL Participants With MaHR
Timepoint [3] 0 0
Up to 6 months after initiation of study treatment
Secondary outcome [1] 0 0
Percentage of CP-CML Participants With CHR
Timepoint [1] 0 0
Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
Secondary outcome [2] 0 0
Percentage of CP-CML Participants With Confirmed MCyR
Timepoint [2] 0 0
Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
Secondary outcome [3] 0 0
Percentage of CP-CML Participants With Major Molecular Response (MMR)
Timepoint [3] 0 0
Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
Secondary outcome [4] 0 0
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MCyR
Timepoint [4] 0 0
Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
Secondary outcome [5] 0 0
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With Confirmed MCyR
Timepoint [5] 0 0
Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
Secondary outcome [6] 0 0
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MMR
Timepoint [6] 0 0
Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
Secondary outcome [7] 0 0
Time to Response
Timepoint [7] 0 0
Up to approximately 48 months after first dose
Secondary outcome [8] 0 0
Duration of Response
Timepoint [8] 0 0
Up to approximately 48 months after first dose
Secondary outcome [9] 0 0
Progression-free Survival (PFS)
Timepoint [9] 0 0
Every 12 weeks ± 2 weeks from last dose of study drug or the investigator/participant decision to discontinue treatment, whichever occurred later (Up to approximately 96 months after last dose)
Secondary outcome [10] 0 0
Overall Survival (OS)
Timepoint [10] 0 0
From the first dose of study treatment until death (Up to 96 months post last dose)
Secondary outcome [11] 0 0
Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Serious AE (SAE)
Timepoint [11] 0 0
From first dose up to 30 days after last dose of the study drug (Up to approximately 49 months)

Eligibility
Key inclusion criteria
* Participants must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL
* Previously treated with and developed resistance or intolerance to dasatinib or nilotinib OR developed the T3151 mutation after any tyrosine kinase inhibitor (TKI) therapy
* =18 years old
* Eastern Cooperative Oncology Group (ECOG) performance status = 2
* Minimum life expectancy of =3 months
* Adequate kidney function
* Adequate liver function
* Normal pancreatic function
* Normal QT Fridericia-corrected interval (QTcF) =450 ms for males and =470 ms for females
* Negative pregnancy test (if woman of childbearing potential)
* Agree to use effective form of contraception (as applicable)
* Ability to comply with study procedures, in the Investigator's opinion
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Received prior TKI treatment within 7 days prior to receiving the first dose of ponatinib, or have not recovered from adverse events (except alopecia) due to agents previously administered.
* Received other therapies as follows:

1. For CML chronic phase (CP) and accelerated phase (AP) participants, received hydroxyurea or anagrelide within 24 hours prior to receiving the first dose of ponatinib; interferon, cytarabine, or immunotherapy within 14 days prior to first dose of ponatinib; or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib.
2. For CML blast phase (BP) participants, received chemotherapy within 14 days prior to the first dose of ponatinib.
3. For Ph+ ALL participants, received corticosteroids within 24 hours before the first dose of ponatinib; or vincristine within 7 days prior to the first dose of ponatinib; or received other chemotherapy within 14 days prior to the first dose of ponatinib.
* Underwent stem cell transplant <60 days prior to receiving first dose of ponatinib
* Evidence of on-going graft versus-host disease (GVHD), or GVHD requiring immunosuppressive therapy
* Taking medications that are known to be associated with Torsades de Pointes
* Require concurrent treatment with immunosuppressive agents (other than corticosteroids prescribed for a short course of therapy)
* Previously treated with ponatinib
* CML CP participants are excluded if they are in Complete cytogenetic response (CCyR)
* Participants with CML AP, CML BP, or Ph+ ALL are excluded if they are in Major Hematologic Response (MaHR).
* Have active Central Nervous System (CNS) disease
* Have significant or active cardiovascular disease
* Have a significant bleeding disorder unrelated to CML or Ph+ALL
* Have a history of pancreatitis or alcohol abuse
* Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
* Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of ponatinib
* Diagnosed with another primary malignancy in the past 3 years
* Pregnant or lactating
* Underwent major surgery within 14 days prior to first dose of ponatinib
* Have ongoing or active infection
* Suffer from any other condition or illness that would compromise safety or interfere with evaluation of the drug

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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,QLD,SA,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Alfred Hospital - Box Hill
Recruitment hospital [5] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Bruxelles
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
France
State/province [3] 0 0
Bordeaux
Country [4] 0 0
France
State/province [4] 0 0
Le Chesnay
Country [5] 0 0
France
State/province [5] 0 0
Lille
Country [6] 0 0
France
State/province [6] 0 0
Nancy
Country [7] 0 0
France
State/province [7] 0 0
Nice
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
France
State/province [9] 0 0
Pierre-Benite
Country [10] 0 0
France
State/province [10] 0 0
Poitiers
Country [11] 0 0
France
State/province [11] 0 0
Toulouse
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Germany
State/province [13] 0 0
Frankfurt
Country [14] 0 0
Germany
State/province [14] 0 0
Jena
Country [15] 0 0
Germany
State/province [15] 0 0
Mannheim
Country [16] 0 0
Germany
State/province [16] 0 0
Munchen
Country [17] 0 0
Italy
State/province [17] 0 0
Bologna
Country [18] 0 0
Italy
State/province [18] 0 0
Modena
Country [19] 0 0
Italy
State/province [19] 0 0
Monza
Country [20] 0 0
Italy
State/province [20] 0 0
Orbassano (TO)
Country [21] 0 0
Italy
State/province [21] 0 0
Roma
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Netherlands
State/province [23] 0 0
Amsterdam
Country [24] 0 0
Netherlands
State/province [24] 0 0
Groningen
Country [25] 0 0
Singapore
State/province [25] 0 0
Singapore
Country [26] 0 0
Spain
State/province [26] 0 0
Barcelona
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid
Country [28] 0 0
Spain
State/province [28] 0 0
Salamanca
Country [29] 0 0
Spain
State/province [29] 0 0
Valencia
Country [30] 0 0
Sweden
State/province [30] 0 0
Lund
Country [31] 0 0
Sweden
State/province [31] 0 0
Stockholm
Country [32] 0 0
Sweden
State/province [32] 0 0
Uppsala
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Glasgow
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Liverpool
Country [35] 0 0
United Kingdom
State/province [35] 0 0
London
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Newcastle
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Nottingham

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Medical 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

TypeCitations or Other Details
Journal Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, ... [More Details]