Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000614493
Ethics application status
Approved
Date submitted
28/11/2007
Date registered
29/11/2007
Date last updated
17/09/2023
Date data sharing statement initially provided
4/08/2023
Date results provided
4/08/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase II study in adult patients with newly-diagnosed chronic myeloid leukaemia of initial intensified Glivec® therapy, and sequential combination therapy for non-responders. With Protocol Amendments October 2004: to include an Extension Phase of the Study
Scientific title
A Phase II study in adult patients with newly-diagnosed chronic myeloid leukaemia of initial intensified Glivec® therapy, and sequential combination therapy for non-responders, in order to assess response and survival
Secondary ID [1] 501 0
Australasian Leukaemia and Lymphoma Group CML6
Universal Trial Number (UTN)
Trial acronym
TIDEL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic myeloid leukaemia (CML) 2594 0
Condition category
Condition code
Cancer 2705 2705 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. All patients receive higher dose imatinib – 600 mg/day
2. in eligible patients dose increased to 800 mg based on time dependent response targets
3. In eligible patients cytosine arabinoside added to imatinib if response targets are not reached
Intervention code [1] 2326 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 3605 0
To assess overall rates and duration of complete cytogenetic response (CCR) and molecular response (MR) achieved using a schedule of intensive, escalated and combination therapy with Glivec, in association with filgrastim support, in adults with newly-diagnosed chronic-phase CML over the 2 year study period.
Timepoint [1] 3605 0
Every 3 months for 8 years
Secondary outcome [1] 6037 0
1. To assess overall rates and duration of response, Quality of Life using European Quality of Life 5 Dimension (EQ-5D) Health Questionnaire and overall survival.
Timepoint [1] 6037 0
Every 3 months for 8 years
Secondary outcome [2] 6038 0
2. To determine the safety and efficacy of filgrastim
Timepoint [2] 6038 0
Every 3 months for 2 years
Secondary outcome [3] 6039 0
3. To determine the patterns of change of CML disease load in blood and/or bone marrow over time
Timepoint [3] 6039 0
Every 3 months for 8 years
Secondary outcome [4] 6040 0
4. To determine the tolerability, quality of life, and safety of initial therapy with Glivec? 600mg daily, and escalated therapy with Glivec 800mg daily, and subsequent combined sequential therapy with Glivec and Cytosine arabinoside
Timepoint [4] 6040 0
Every 3 months for 8 years
Secondary outcome [5] 6041 0
5. To assess subsequent levels of response to imatinib in patients who show continuing response at 24 months on Study, by Quantitative Polymerase Chain Reaction (Q-PCR) analysis of 3-monthly blood samples for the ratio of BCR-ABL/BCRL transcripts, for up to six further years of an Extension Phase to this Study.
Timepoint [5] 6041 0
Every 3 months for 8 years
Secondary outcome [6] 6042 0
6. To evaluate reasons for loss of response to imatinib in patients on the Extension Phase of this Study, if and when Q-PCR analysis of 3-monthly blood samples (for up to six further years) shows a 2-fold increase in bcr-abl transcripts, by mutation analyses of BCR-ABL genes.
Timepoint [6] 6042 0
Every 3 months for 8 years

Eligibility
Key inclusion criteria
1.Male or female patients between 16 and 75 years of age inclusive. Patients must have all of the following:
2.i.be enrolled within 6 months of initial diagnosis of CML-CP
ii.be previously untreated for CML with the exception of hydroxyurea and/or anagrelide,
iii.cytogenetic confirmation of Philadelphia chromosome or variants of (9;22) translocations; OR molecular (PCR) confirmation of bcr-abl gene rearrangement(s);
iv.(a) < 15% blasts in peripheral blood and bone marrow;
(b) < 30% blasts plus promyelocytes in peripheral blood and bone marrow;
(c) < 20% basophils in peripheral blood,
(d) > 100 x 109/L platelets
v.no evidence of extramedullary leukemic involvement, with the exception of the spleen and liver,
3.Written voluntary informed consent.
4.Patients with an Eastern Cooperative Oncology Group performance status score of 2 or less.
5.Patients with serum bilirubin, Serum glutamic oxaloacetic transaminase, Serum glutamic pyruvic transaminase and creatinine concentrations <1.5x the institutional upper limits of normal (ULN).
6.Patients with a coagulation international normalised ratio (INR) and a partial thromboplastin time (PTT) <1.5x the institutional ULN, with the exception of allowing inclusion of patients on oral anticoagulant therapy.
Minimum age
16 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Patients who have received other investigational agents.
2.Patients with secondary chromosomal abnormalities in their CML cells.
3.Patients who received prior chemotherapy. Previous treatment with hydroxyurea is allowed.
4.Patients with uncontrolled medical disease
5.Patients with a positive test for human immunodeficiency virus
6.Patients who have undergone major surgery within 4 weeks of Study Day 1, or who have not recovered from prior major surgery.
7.Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to Study Day 1, and (d) male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial (postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential).
8.Patients with a history of another malignancy within the past five years, with the exception of adequately-treated basal or squamous cell skin carcinoma or cervical carcinoma in situ.
9.Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.

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
21/10/2002
Actual
21/10/2002
Date of last participant enrolment
Anticipated
Actual
27/08/2003
Date of last data collection
Anticipated
Actual
16/02/2006
Sample size
Target
100
Accrual to date
Final
103
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 2837 0
Commercial sector/Industry
Name [1] 2837 0
Novartis Australia
Country [1] 2837 0
Australia
Funding source category [2] 2838 0
Commercial sector/Industry
Name [2] 2838 0
Amgen Australia
Country [2] 2838 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
c/- Centre for Biostatistics and Clinical Trials
Peter MacCallum Cancer Centre
St Andrews Place
East Melbourne VIC 3002
Country
Australia
Secondary sponsor category [1] 2560 0
None
Name [1] 2560 0
Address [1] 2560 0
Country [1] 2560 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4769 0
Royal Adelaide Hospital
Ethics committee address [1] 4769 0
Ethics committee country [1] 4769 0
Australia
Date submitted for ethics approval [1] 4769 0
Approval date [1] 4769 0
09/10/2002
Ethics approval number [1] 4769 0
Ethics committee name [2] 4770 0
Albury Base Hospital/Murray Valley Private Hospital
Ethics committee address [2] 4770 0
Ethics committee country [2] 4770 0
Australia
Date submitted for ethics approval [2] 4770 0
Approval date [2] 4770 0
Ethics approval number [2] 4770 0
Ethics committee name [3] 4771 0
Alfred Hospital
Ethics committee address [3] 4771 0
Ethics committee country [3] 4771 0
Australia
Date submitted for ethics approval [3] 4771 0
Approval date [3] 4771 0
Ethics approval number [3] 4771 0
Ethics committee name [4] 4772 0
Fremantle Hospital
Ethics committee address [4] 4772 0
Ethics committee country [4] 4772 0
Australia
Date submitted for ethics approval [4] 4772 0
Approval date [4] 4772 0
Ethics approval number [4] 4772 0
Ethics committee name [5] 4773 0
Newcastle Mater Hospital
Ethics committee address [5] 4773 0
Ethics committee country [5] 4773 0
Australia
Date submitted for ethics approval [5] 4773 0
Approval date [5] 4773 0
Ethics approval number [5] 4773 0
Ethics committee name [6] 4774 0
Brisbane Mater Hospital
Ethics committee address [6] 4774 0
Ethics committee country [6] 4774 0
Australia
Date submitted for ethics approval [6] 4774 0
Approval date [6] 4774 0
Ethics approval number [6] 4774 0
Ethics committee name [7] 4775 0
Monash Medical Centre
Ethics committee address [7] 4775 0
Ethics committee country [7] 4775 0
Australia
Date submitted for ethics approval [7] 4775 0
Approval date [7] 4775 0
Ethics approval number [7] 4775 0
Ethics committee name [8] 4776 0
Peter MacCallum Cancer Centre
Ethics committee address [8] 4776 0
Ethics committee country [8] 4776 0
Australia
Date submitted for ethics approval [8] 4776 0
Approval date [8] 4776 0
Ethics approval number [8] 4776 0
Ethics committee name [9] 4777 0
Prince of Wales Hospital
Ethics committee address [9] 4777 0
Ethics committee country [9] 4777 0
Australia
Date submitted for ethics approval [9] 4777 0
Approval date [9] 4777 0
Ethics approval number [9] 4777 0
Ethics committee name [10] 4778 0
Princess Alexandra Hospital
Ethics committee address [10] 4778 0
Ethics committee country [10] 4778 0
Australia
Date submitted for ethics approval [10] 4778 0
Approval date [10] 4778 0
Ethics approval number [10] 4778 0
Ethics committee name [11] 4779 0
Royal Brisbane Hospital
Ethics committee address [11] 4779 0
Ethics committee country [11] 4779 0
Australia
Date submitted for ethics approval [11] 4779 0
Approval date [11] 4779 0
22/11/2002
Ethics approval number [11] 4779 0
Ethics committee name [12] 4780 0
Royal Melbourne Hospital
Ethics committee address [12] 4780 0
Ethics committee country [12] 4780 0
Australia
Date submitted for ethics approval [12] 4780 0
Approval date [12] 4780 0
Ethics approval number [12] 4780 0
Ethics committee name [13] 4781 0
Royal North Shore Hospital
Ethics committee address [13] 4781 0
Ethics committee country [13] 4781 0
Australia
Date submitted for ethics approval [13] 4781 0
Approval date [13] 4781 0
14/10/2002
Ethics approval number [13] 4781 0
Ethics committee name [14] 4782 0
Royal Perth Hospital
Ethics committee address [14] 4782 0
Ethics committee country [14] 4782 0
Australia
Date submitted for ethics approval [14] 4782 0
Approval date [14] 4782 0
21/11/2002
Ethics approval number [14] 4782 0
Ethics committee name [15] 4783 0
Sir Charles Gairdner Hospital
Ethics committee address [15] 4783 0
Ethics committee country [15] 4783 0
Australia
Date submitted for ethics approval [15] 4783 0
Approval date [15] 4783 0
Ethics approval number [15] 4783 0
Ethics committee name [16] 4784 0
St Vincent's Hospital Melbourne
Ethics committee address [16] 4784 0
Ethics committee country [16] 4784 0
Australia
Date submitted for ethics approval [16] 4784 0
Approval date [16] 4784 0
18/11/2004
Ethics approval number [16] 4784 0
Ethics committee name [17] 4785 0
St Vincent's Hospital Sydney
Ethics committee address [17] 4785 0
Ethics committee country [17] 4785 0
Australia
Date submitted for ethics approval [17] 4785 0
Approval date [17] 4785 0
Ethics approval number [17] 4785 0
Ethics committee name [18] 4786 0
Westmead Hospital
Ethics committee address [18] 4786 0
Ethics committee country [18] 4786 0
Australia
Date submitted for ethics approval [18] 4786 0
Approval date [18] 4786 0
02/03/2005
Ethics approval number [18] 4786 0

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

Contacts
Principal investigator
Name 28219 0
A/Prof A.Prof. T Hughes, A.Prof. A Grigg
Address 28219 0
:Institute of Medical and Veterinary Science,
Frome Road, Adelaide SA 5000. Postal address: PO Box 14 Rundle Mall SA 5000
Country 28219 0
Australia
Phone 28219 0
+61 08 82223330
Fax 28219 0
Email 28219 0
[email protected]
Contact person for public queries
Name 11376 0
Timothy Hughes
Address 11376 0
Division of Haematology
Institute of Medical and Veterinary Science
Frome Road
Adelaide SA 5000
Country 11376 0
Australia
Phone 11376 0
+61 8 82223330
Fax 11376 0
+61 8 82223139
Email 11376 0
[email protected]
Contact person for scientific queries
Name 2304 0
Timothy Hughes
Address 2304 0
Division of Haematology
Institute of Medical and Veterinary Science
Frome Road
Adelaide SA 5000
Country 2304 0
Australia
Phone 2304 0
+61 8 82223330
Fax 2304 0
+61 8 82223139
Email 2304 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?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIImpact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy2008https://doi.org/10.1182/blood-2008-06-161737
Dimensions AIEarly molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML2013https://doi.org/10.1182/blood-2012-10-462291
N.B. These documents automatically identified may not have been verified by the study sponsor.