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Trial registered on ANZCTR


Registration number
ACTRN12620000851965
Ethics application status
Approved
Date submitted
1/06/2020
Date registered
27/08/2020
Date last updated
1/06/2024
Date data sharing statement initially provided
27/08/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A study for patients with newly diagnosed Chronic Phase Myeloid Leukaemia evaluating the drug Asciminib.
Scientific title
An Australasian Leukaemia and Lymphoma Group (ALLG) single arm phase II study to evaluate the efficacy of asciminib in newly diagnosed patients with chronic phase chronic myeloid leukaemia.
Secondary ID [1] 301030 0
Nil
Universal Trial Number (UTN)
Trial acronym
CML13
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukaemia 317086 0
Condition category
Condition code
Cancer 315251 315251 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All eligible patients will receive Asciminib 40mg twice a day (oral tablet) for up to five years.

Peripheral Blood/Bone Marrow will be analysed at the following timepoints and reviewed by the treating physician.
3, 6, 12 and 18 months.
Depending on the results, the asciminb dose may increase to 80mg twice a day, stay the same or stay the same and include another medication. The choice of additional medication will be at the investigators discretion.
Participants with BCR-ABL greater than 10% at 3 months, or with BCR-ABL greater than 1% at 12 months, will continue to receive asciminib, with the addition of another medication.
Participants who fail to achieve BCR-ABL less than or equal to 1% at 6 months, BCR-ABL less than or equal to 0.1% at 12 months or BCR-ABL less than or equal to 0.01% at 18 months will have asciminib dose escalation to 80mg BID if they are on asciminib monotherapy.


Participants will remain on treatment if well tolerated determined by treating physician for 5 years.
Intervention code [1] 317341 0
Treatment: Drugs
Comparator / control treatment
No control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323984 0
The primary outcome measure will be to assess the Early molecular response, or EMR, defined as the proportion of patients who achieve BCR-ABL less than 10% IS.
Timepoint [1] 323984 0
This will be assessed by a blood test at 3 months after starting treatment.
Primary outcome [2] 323985 0
The primary outcome measure will be to assess the Major molecular response, or MMR (BCR-ABL less than 0.1% IS). The outcome will be assessed by analysing peripheral blood and bone marrow.
Timepoint [2] 323985 0
This will be assessed at 12 months from starting treatment.
Secondary outcome [1] 383492 0
A secondary outcome measure will be to assess the safety and tolerability of the drug by reviewing the reported patients adverse events such as tiredness, nausea, headache's etc
Timepoint [1] 383492 0
This will be reviewed ongoing throughout the intervention period for a maximum of 5 years following the start of the intervention treatment, by monitoring patient medical records.
Secondary outcome [2] 383495 0
A secondary outcome measure will be to monitor the overall survival of patients receiving treatment. Patient medical records and death report will be reviewed.
Timepoint [2] 383495 0
This will be reviewed at the end of the intervention period, a maximum of 5 years following the start of the intervention treatment.
Secondary outcome [3] 385127 0
A secondary outcome will be to assess the safety and tolerability of the drug by reviewing the number of patients who come off treatment due to an adverse event' as a secondary outcome. This will be assessed by reviewing patients Case Report Forms (CRF) which would detail the reasons for coming off treatment.and patient medical records.
Timepoint [3] 385127 0
This will be reviewed ongoing throughout the intervention period for a maximum of 5 years following the start of the intervention treatment, by monitoring patient medical records.

Eligibility
Key inclusion criteria
1. Newly diagnosed CML-CP patients aged 18 or older
a) Prior ABP-TKI exposure greater than 14 days is not permitted.
i) Hydroxyurea or anagrelide treatment permitted prior to commencing asciminib (this may be continued for up to 1 week after commencing study treatment)
ii) Leukapheresis allowed as indicated
b) Must be equal to or less than 6 months from diagnosis to screening
c) Must have e13a2 and/or e14a2 transcript on screening BCR-ABL QPCR. Transcript e1a2 also permitted.
d) Must have bone marrow confirming chronic phase as per ELN (not WHO) criteria.
e) Additional cytogenetic abnormalities at baseline or diagnosis do not classify a patient as accelerated phase for the purpose of this study.
2. Willingly provide informed consent and agree to comply with study protocol
3. ECOG performance status 0-2
4. Based on known medical history, expected to have a life expectancy of greater thsn or equal to 12 months
5. Eligible for reimbursed treatment with imatinib, dasatinib or nilotinib under the PBS complex drug program in Australia, the Pharmac system in New Zealand, or through other arrangements with regulatory and funding authorities (compassionate supply or hospital funded supply).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Major surgery within 2 weeks of, or having not recovered from surgery, by the time of screening.
2. Abnormal clinical laboratory results (re-screening allowed)
a) Total bilirubin greater than 1.5x ULN (in patients with Gilbert’s syndrome, total bilirubin greater than 3x ULN, or direct bilirubin greater than 1.5x ULN)
b) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3x ULN.
c) Alkaline phosphatase greater than 2.5 times the ULN unless considered to be not of hepatic origin
d) Creatinine greater than 1.5 times ULN
e) Amylase / Lipase values greater than 1.5 times institutional ULN
3. Treatment with strong inducers of CYP3A4/5, CYP2C8 and CYP2C9 (See Appendix 1 for list of prohibited drugs). Consumption of grapefruit, Seville oranges, star fruit and their juice / derivatives / products is not permitted whilst a patient is taking study medication.
4. Active infection requiring systemic therapy at the time of screening
5. History of significant congenital or acquired bleeding disorder unrelated to cancer.
6. Known human immunodeficiency virus (HIV) positive (testing to exclude infection is not required in the absence of suggestive history)
7. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
8. Corrected QT interval (QTc) of greater than 480 milliseconds (ms) on baseline electrocardiogram (ECG) (using corrected QT interval using Fridericia [QTcF]).
9. Uncontrolled cardiovascular condition, including ongoing cardiac arrhythmias (e.g. ventricular arrhythmias or Torsades de Pointe, or third degree heart block without pace maker insertion); congestive heart failure, angina, or myocardial infarction within the past 3 months prior to screening.
10. Other concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol.
11. Cytopathologically confirmed CNS infiltration. (In the absence of suspicion of CNS involvement, lumbar puncture is not required.)
12. A history of concomitant primary malignant disease that requires active cytotoxic treatment and / or a life limiting illness expected to have a life expectancy less than 5 years.
13. History of acute pancreatitis within 1 year of study entry, chronic pancreatitis, or any ongoing pancreatic disease.
14. Acute or chronic active liver disease. HBV core antibody positivity is not an automatic exclusion.
15. Subjects unable to comply with requirements for contraception as per study requirements.
16. Prior stem cell transplantation.
17. Reproductive status
a) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
b) Women must not be breastfeeding.
c) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug, plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion.
d) Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion. (See appendix 4)
e) Azoospermic males are exempt from contraceptive requirements.
18. Current participation in another therapeutic clinical trial (participation in clinical trials that do not involve active interventions is not an exclusion for the study).

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
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/11/2020
Actual
15/12/2020
Date of last participant enrolment
Anticipated
1/11/2022
Actual
24/11/2022
Date of last data collection
Anticipated
24/11/2027
Actual
Sample size
Target
100
Accrual to date
Final
101
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 19113 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 19114 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 19115 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 19116 0
Concord Repatriation Hospital - Concord
Recruitment hospital [5] 19117 0
Royal Perth Hospital - Perth
Recruitment hospital [6] 19118 0
Royal Hobart Hospital - Hobart
Recruitment hospital [7] 19119 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [8] 19120 0
Gosford Hospital - Gosford
Recruitment hospital [9] 19122 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [10] 19123 0
Liverpool Hospital - Liverpool
Recruitment hospital [11] 19124 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [12] 19125 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [13] 19126 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [14] 24149 0
Wellington Health Service - Wellington
Recruitment postcode(s) [1] 33672 0
5000 - Adelaide
Recruitment postcode(s) [2] 33673 0
5042 - Bedford Park
Recruitment postcode(s) [3] 33674 0
3000 - Melbourne
Recruitment postcode(s) [4] 33675 0
2139 - Concord
Recruitment postcode(s) [5] 33676 0
6000 - Perth
Recruitment postcode(s) [6] 33677 0
7000 - Hobart
Recruitment postcode(s) [7] 33678 0
3168 - Clayton
Recruitment postcode(s) [8] 33679 0
2250 - Gosford
Recruitment postcode(s) [9] 33681 0
4029 - Herston
Recruitment postcode(s) [10] 33682 0
2170 - Liverpool
Recruitment postcode(s) [11] 33683 0
6150 - Murdoch
Recruitment postcode(s) [12] 33684 0
3065 - Fitzroy
Recruitment postcode(s) [13] 33685 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 22602 0
New Zealand
State/province [1] 22602 0

Funding & Sponsors
Funding source category [1] 305475 0
Commercial sector/Industry
Name [1] 305475 0
Novartis Pharmaceuticals Australia Pty Limited
Country [1] 305475 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australiasian Leukaemia and Lymphoma Group
Address
35 Elizabeth St
Richmond
Vic
3121
Country
Australia
Secondary sponsor category [1] 305873 0
None
Name [1] 305873 0
Address [1] 305873 0
Country [1] 305873 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305791 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 305791 0
Ethics committee country [1] 305791 0
Australia
Date submitted for ethics approval [1] 305791 0
03/08/2020
Approval date [1] 305791 0
21/09/2020
Ethics approval number [1] 305791 0
R20200803

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

Contacts
Principal investigator
Name 101606 0
Dr David Yeung
Address 101606 0
Royal Adelaide Hospital
Port Road, Adelaide SA 5000
Country 101606 0
Australia
Phone 101606 0
+61 3 8373 9701
Fax 101606 0
Email 101606 0
david.yeung@adelaide.edu.au
Contact person for public queries
Name 101607 0
Delaine Smith
Address 101607 0
Australasian Leukaemia and Lymphoma Group (ALLG)
35 Elizabeth St
Richmond
Vic
3121
Country 101607 0
Australia
Phone 101607 0
+61 3 8373 9701
Fax 101607 0
Email 101607 0
delaine.smith@allg.org.au
Contact person for scientific queries
Name 101608 0
Delaine Smith
Address 101608 0
Australasian Leukaemia and Lymphoma Group (ALLG)
35 Elizabeth St
Richmond
Vic
3121
Country 101608 0
Australia
Phone 101608 0
+61 3 8373 9701
Fax 101608 0
Email 101608 0
delaine.smith@allg.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patient data will not be shared publically. Aggregate patient data and final results will be presented in the final report.


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
EmbaseAsciminib: First Approval.2022https://dx.doi.org/10.1007/s40265-021-01662-3
EmbaseAsciminib as a third line option in chronic myeloid leukemia.2023https://dx.doi.org/10.1007/s12185-022-03432-7
N.B. These documents automatically identified may not have been verified by the study sponsor.