ActivePhase 2ACTRN12620000851965

A study for patients with newly diagnosed Chronic Phase Myeloid Leukaemia evaluating the drug Asciminib.

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.

Sponsor

Australiasian Leukaemia and Lymphoma Group

Enrollment

100 participants

Start Date

Dec 14, 2020

Study Type

Interventional

Conditions

Chronic Myeloid Leukaemia

Summary

This purpose of this study is to evaluate the efficacy of asciminib in newly diagnosed patients with chronic phase chronic myeloid leukaemia. Who is it for? You may be eligible for this study if you are an adult who has been newly diagnosed with chronic phase chronic myeloid leukaemia. Study details Eligible participants in this study will receive asciminb 40mg (oral) twice a day for up to five years. Dose reduction or increase may occur depending on the patients tolerability and blood results. The investigator will review every 3 months. During the trial patients will have blood tests performed and bone marrow samples taken to help determined the progress of the treatment. It is hoped that this research will help determine the efficacy of this treatment, and what kinds of side effects/complications may occur with this treatment.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria12

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.
Willingly provide informed consent and agree to comply with study protocol
ECOG performance status 0-2
Based on known medical history, expected to have a life expectancy of greater thsn or equal to 12 months
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).

Exclusion Criteria28

Major surgery within 2 weeks of, or having not recovered from surgery, by the time of screening.
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
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.
Active infection requiring systemic therapy at the time of screening
History of significant congenital or acquired bleeding disorder unrelated to cancer.
Known human immunodeficiency virus (HIV) positive (testing to exclude infection is not required in the absence of suggestive history)
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Corrected QT interval (QTc) of greater than 480 milliseconds (ms) on baseline electrocardiogram (ECG) (using corrected QT interval using Fridericia [QTcF]).
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.
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.
Cytopathologically confirmed CNS infiltration. (In the absence of suspicion of CNS involvement, lumbar puncture is not required.)
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.
History of acute pancreatitis within 1 year of study entry, chronic pancreatitis, or any ongoing pancreatic disease.
Acute or chronic active liver disease. HBV core antibody positivity is not an automatic exclusion.
Subjects unable to comply with requirements for contraception as per study requirements.
Prior stem cell transplantation.
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.
Current participation in another therapeutic clinical trial (participation in clinical trials that do not involve active interventions is not an exclusion for the study).

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Interventions

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 trea

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.