AMLM22/D3 - The International Acute myeloid leukaemia (AML) Platform Consortium (IAPC) trial is a randomised, multi-arm study platform to compare the efficacy of experimental therapies versus standard of care in patients with acute myeloid leukaemia in first complete remission.
AMLM22/D3-The International Acute myeloid leukaemia (AML) Platform Consortium (IAPC) trial is a randomised, multi-arm study platform to compare the efficacy of experimental therapies versus standard of care in subjects with acute myeloid leukaemia in first complete remission. Domain 3 is investigating the safety and efficacy of an Astrazeneca drug labelled AZD5153 as a maintenance therapy option.
Australian Leukaemia and Lymphoma Group (ALLG)
50 participants
Apr 30, 2021
Interventional
Conditions
Summary
This study will evaluate the safety and efficacy of AZD5153 for Acute Myeloid Leukemia in the maintenance setting. Who is it for? You may be eligible to join this study if you are aged 16 and above and have Acute Myeloid Leukemia in first complete remission. Study details This study is part of the International AML Platform Consortium. Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will receive standard care which is generally observation. Participants in the other group will receive the drug AZD5153 daily for a total of upto 24 months. As part of the study, participants will have blood tests at the start of each cycle (every 21 days) as well as an ECG to monitor heart function. AZD5153 is known to have adverse effects on the heart therefore, participants will also have a MUGA (Multiple Gated Acquisition scan) at screening. We hope that the results from this trial will be used to help these new treatments which may be better for people with AML than what is currently available ,become accessible to the general population at faster than the normal process.
Eligibility
Inclusion Criteria4
- Provision of written informed consent
- Provision of written informed consent to the ALLG NBCR
- Age 18+ (Age 16-17 permitted if consent for minor PICF approved by the authorizing HREC)
- AML (excluding APL) in first complete remission with bone marrow blasts <5%
Exclusion Criteria18
- Chemotherapy or investigational agents within 28 days of planned study cycle 1 day 1
- History of other malignancy requiring active systemic treatment or which is likely to result in an expected survival time of less than 2 years
- Viral infection with known HIV or viral hepatitis type B or C not adequately controlled by antiviral medication
- Prior bone marrow or stem cell transplantation
- Platelet count greater than or equal to 100 x 10^9 /L
- Increased bleeding risk as a result of:
- a. Use of parenteral anticoagulants at therapeutic levels, warfarin or direct oral anticoagulants within 14 days prior to the first dose of AZD5153.
- b. Coagulation parameters (prothrombin time/international normalised ratio [PT/INR] and activated partial thromboplastin time [APTT]) less than or equal to 1.5 x upper limit of normal (ULN)
- Cardiac abnormalities as evidenced by any of the following:
- a. Clinically significant conduction abnormalities or uncontrolled arrhythmia.
- b. Uncontrolled hypertension
- c. Greater than or equal to New York Heart Association (NYHA) class II congestive cardiac failure and/or left ventricular ejection fraction < 50% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
- d. ECG findings demonstrating baseline a QTcF interval greater than or equal to 450 ms
- Subject not able to comply with domain-specific contraception recommendations below:
- a. Female patients must use two highly effective contraceptive measures. All methods of contraception (with the exception of total abstinence) should be used in combination with the use of a condom by a male sexual partner for intercourse.
- b. Female patients must not be breast-feeding and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
- i. Post-menopausal women defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatment.
- ii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation.
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Interventions
Domain 3 is AMLM22/D3, will determine the safety and efficacy of AZD5153 and it will be conducted in two stages: Stage 1: A safety run-in stage will confirm the planned optimal dose schedule. At least 9 and up to 18 patients will be enrolled in cohorts of 3 patients. If initial dose level of AZD5153 is deemed intolerable, other dose levels will be explored. Decisions to escalate or de-escalate the dose and the identification of the optimal dose will be guided by use of a Bayesian Optimal Interval (BOIN) design. Stage 2: Once the safety run-in phase is satisfactorily completed, patients will be randomised to either treatment arm 1:AZD5153 (casules; taken orally)at the identified optimal dose or treatment arm 2:standard of care (clinical observation) will commence. Each treatment cycle will be 21days or 28days Dose level +2 40 mg daily for 14 days of 21 day cycle or 40 mg daily for 14 days of 28 day cycle Dose level +1 30 mg daily for 14 days of 21 day cycle or 30 mg daily for 14 days of 28 day cycle Starting dose 20 mg daily for 14 days of 21 day cycle or 20 mg daily for 14 days of 28 day cycle Dose level -1 15 mg daily for 14 days of 21 day cycle or 15 mg daily for 14 days of 28 day cycle Dose level -2 10 mg daily for 14 days of 21 day cycle or 10 mg daily for 14 days of 28 day cycle Dose level -3 5 mg twice daily for 14 days of 21 day cycle or 5 mg twice daily for 14 days of 28 day cycle
Locations(1)
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ACTRN12621000246886