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Trial registered on ANZCTR


Registration number
ACTRN12607000325404
Ethics application status
Approved
Date submitted
15/06/2007
Date registered
18/06/2007
Date last updated
4/08/2023
Date data sharing statement initially provided
30/07/2019
Date results information initially provided
30/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II study in adult patients with newly diagnosed chronic-phase chronic myeloid leukaemia of initial intensified imatinib therapy and sequential dose-escalation followed by treatment with nilotinib in suboptimal responders to determine the rate and duration of major molecular response
Scientific title
A Phase II study in adult patients with newly diagnosed chronic-phase chronic myeloid leukaemia of initial intensified imatinib therapy and sequential dose-escalation followed by treatment with nilotinib in suboptimal responders to determine the rate and duration of major molecular response
Secondary ID [1] 373 0
Australasian Leukaemia and Lymphoma Group (ALLG): ALLG CML9
Universal Trial Number (UTN)
Trial acronym
TIDEL II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
newly-diagnosed chronic phase chronic myeloid leukaemia 1874 0
Condition category
Condition code
Cancer 1968 1968 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients commence imatinib at 600 mg/day. Dose is escalated to 800 mg/day if the trough imatinib plasma level is less than 1000 ng/ml on day 22. Dose is increased to 800 mg/day if the Real-Time Quantitative Polymerase Chain Reaction (RQ-PCR) values of BCR-ABL are >10% at 3 months, >1% at 6 months or >0.1% at 12 months. Dose is switched to nilotinib 400 mg/day if a patient is unable to dose escalate to 800 mg after 1 month of trying or if the BCR-ABL value is >10% at 6 months, >1% at 9 months or >0.1% at 15 months.
Intervention code [1] 1831 0
Treatment: Drugs
Comparator / control treatment
-
Control group
Uncontrolled

Outcomes
Primary outcome [1] 2782 0
To determine the rates of major molecular response (MMR), as determined by RQ-PCR
Timepoint [1] 2782 0
At 12 and 24 months
Primary outcome [2] 2783 0
To estimate the duration of MMR.
Timepoint [2] 2783 0
At 12 and 24 months
Secondary outcome [1] 4696 0
1. To determine rates and duration of major molecular response in patients who switch to nilotinib therapy on study.
Timepoint [1] 4696 0
-
Secondary outcome [2] 4697 0
2. To assess overall rates of complete molecular response (CMR).
Timepoint [2] 4697 0
Achieved on study at 12 and 24 months.

Eligibility
Key inclusion criteria
1. Post-pubertal patients who weigh 40kg or over. 2. Newly diagnosed (within six months of study entry) chronic phase, Philadelphia chromosome-positive Chronic Myeloid Leukaemia (Ph+ CML-CP) involving a BCR-ABL transcript known to be quantifiable.3. No prior therapy for CML and no other current anti-leukaemic therapies (other than prior or current treatment with hydroxyurea or anagrelide).4. No signs of extramedullary leukaemia, except for hepatosplenomegaly.5. Documented chronic-phase CML as defined by:6. Eastern Cooperative Oncology Group Performance Status score <2 7. Patients must have the following laboratory values:a) Potassium level > lower limit of normalb) Calcium (corrected for serum albumin) > lower limit of normalc) Magnesium level > lower limit of normald) Phosphorus > lower limit of normale) ALT and AST < 2.5 × upper limit of normal or < 5.0 × upper limit of normal if considered due to tumourf) ALP < 2.5 × upper limit of normal unless considered due to tumourg) Bilirubin < 1.5 × upper limit of normalh) Creatinine < 1.5 × upper limit of normali) Amylase and lipase < 1.5 × upper limit of normal8. a) Female patients of childbearing potential must have a negative pregnancy test within one week prior to study entry OR have been amenorrhoeic for at least two years. b) All patients of reproductive potential must agree to use birth control for the duration of the study.9. Life expectancy of more than 12 months in the absence of any intervention10. Patient has given written, informed consent to participate in the study
Minimum age
15 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have previously received radiotherapy to >25% of their bone marrow.2. Patients who have undergone major surgery within the 4 weeks prior to study entry or have not recovered from earlier surgery.4 Impaired cardiac function5 Treatment with agents (other than warfarin) that prolong QT interval or inhibit CYP3A4, unless judged to be clinically essential. 6 Patients with international normalized ratio (INR) or activated partial thromboplastin time (APTT) >1.5 x upper limit of normal, except for patients requiring anticoagulants. 7 Cytokine therapy within 4 weeks prior to study entry.8 Another primary malignant disease, except for such conditions that do not currently require treatment9 Impaired gastro-intestinal function or gastro-intestinal disease that may alter imatinib/nilotinib absorption.10 Acute or chronic hepatic or renal disease considered unrelated to cancer.11 Occurrence of pancreatitis within six months of study entry. 12 Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol.13 Cytopathologically confirmed central nervous system infiltration 14 Patients unwilling or unable to comply with protocol and patients with a history of non-compliance or inability to grant informed consent.15 Known diagnosis of human immunodeficiency virus (HIV) infection.16 Prior allogeneic stem cell transplantation. 17 Current participation in another therapeutic clinical trial.

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
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2007
Actual
15/11/2007
Date of last participant enrolment
Anticipated
Actual
25/03/2011
Date of last data collection
Anticipated
Actual
31/10/2016
Sample size
Target
150
Accrual to date
Final
210
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 2108 0
Commercial sector/Industry
Name [1] 2108 0
Novartis Australia
Country [1] 2108 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
-
Country
Australia
Secondary sponsor category [1] 1915 0
None
Name [1] 1915 0
none
Address [1] 1915 0
Country [1] 1915 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303954 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 303954 0
Level 3, Roma Mitchell House
136 North Terrace, ADELAIDE SA 5000
Ethics committee country [1] 303954 0
Australia
Date submitted for ethics approval [1] 303954 0
12/07/2007
Approval date [1] 303954 0
15/08/2007
Ethics approval number [1] 303954 0
070718

Summary
Brief summary
This trial tests the hypothesis that molecular response can be maximised by a combined approach of higher dose imatinib for all de-novo CML patients plus a rapid switch to nilotinib in patients who are intolerant or have suboptimal response to imatinib.
Trial website
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 27645 0
Prof Timothy Hughes
Address 27645 0
SA Pathology (RAH Campus)
Frome Road, Adelaide SA 5000
Country 27645 0
Australia
Phone 27645 0
+61 8 8222 3330
Fax 27645 0
Email 27645 0
[email protected]
Contact person for public queries
Name 11020 0
Timothy Hughes
Address 11020 0
Division of Haematology, Institute of medical and Veterinary Science
Frome road
Adelaide 5000 SA
Country 11020 0
Australia
Phone 11020 0
08 82223330
Fax 11020 0
08 82223855
Email 11020 0
[email protected]
Contact person for scientific queries
Name 1948 0
Timothy Hughes
Address 1948 0
Division of Haematology, Institute of medical and Veterinary Science
Frome road
Adelaide 5000 SA
Country 1948 0
Australia
Phone 1948 0
08 82223330
Fax 1948 0
08 82223855
Email 1948 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified IPD data, for all data collected during the trial
When will data be available (start and end dates)?
Data available 3 months following publication, for an indefinite period
Available to whom?
Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted.
Available for what types of analyses?
Any type of analysis
Assessed on a case-by-case basis
How or where can data be obtained?
Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19914Study protocol  [email protected] Access can be requested via the Health Data Austra... [More Details]



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes TIDEL-II: first-line use of imatinib in CML with e... [More Details] 82094-(Uploaded-23-07-2019-13-44-05)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEarly molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML.2013https://dx.doi.org/10.1182/blood-2012-10-462291
EmbaseTIDEL-Ii: First-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets.2015https://dx.doi.org/10.1182/blood-2014-07-590315
EmbaseTGF-alpha and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy.2016https://dx.doi.org/10.1038/leu.2016.34
EmbaseA Method for Next-Generation Sequencing of Paired Diagnostic and Remission Samples to Detect Mitochondrial DNA Mutations Associated with Leukemia.2017https://dx.doi.org/10.1016/j.jmoldx.2017.05.009
Dimensions AIModelling Predictors of Molecular Response to Frontline Imatinib for Patients with Chronic Myeloid Leukaemia2017https://doi.org/10.1371/journal.pone.0168947
EmbaseWidespread aberrant alternative splicing despite molecular remission in chronic myeloid leukaemia patients.2020https://dx.doi.org/10.3390/cancers12123738
EmbaseAdverse outcomes for chronic myeloid leukemia patients with splenomegaly and low in vivo kinase inhibition on imatinib.2023https://dx.doi.org/10.1038/s41408-023-00917-4
N.B. These documents automatically identified may not have been verified by the study sponsor.