A multi-arm trial for patients with acute myeloid leukaemia investigating new treatments which target early relapse and changes in disease characteristics – MBG453 OR MBG453 and Azacitidine
Leukaemia – Acute leukaemia
This is an investigational agent within the ALLG AMLM26 INTERCEPT trial platform, which is registered on ANZCTR with ID ACTRN12621000439842. This investigational agent (MBG453 – a new treatment) will be evaluated for its activity alone and in combination with azacitidine in a population of participants with progressive acute myeloid leukemia (AML).
In order to be eligible to the MBG453 treatment arms inclusion criteria includes:
– meet MRD eligibility for INTERCEPT therapy based on a screening sample taken no more than 28 days prior to cycle 1 of day 1 of treatment on this treatment arm. (An increase of MRD greater than or equal to 1 log from nadir to at least 0.01%, confirmed with a repeat central sample.) Eligibility will be confirmed by the MRD review committee.
– Patients entering this arm post-allogeneic stem cell transplantation will need to have an absolute lymphocyte count of greater than or equal to 0.2 x 109/L and no evidence of active acute graft-versus-host disease (GVHD)
– Subject must have adequate renal function as demonstrated by a creatinine clearance greater than or equal to 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hours urine collection
-Subject must have adequate liver function as demonstrated by:
– aspartate aminotransferase (AST) less than or equal to 3.0 × ULN
– alanine aminotransferase (ALT) less than or equal to 3.0 × ULN
– bilirubin less than or equal to 1.5 × ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin)
– agree to follow the recommended contraception procedures
In order to be eligible to the MBG453 treatment arms exclusion criteria includes:
– Prior allogeneic stem cell transplantation within 3 months of post-conditioning or on greater than or equal to 10mg/day prednisolone for graft vs host disease
– QT-interval corrected according to Fridericia’s formula (QTcF) greater than 470ms (except for right bundle branch block)
– Subject is HIV positive
– Patients with greater than or equal to 5% myeloblasts in bone marrow on morphologic assessment
– Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
a. Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
b. Acute/Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment.
– Systemic chronic corticosteroid therapy (greater than or equal to 10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
– For initial enrolment to INTERCEPT therapy, patients who have received previous TIM3 inhibitor treatment are excluded. This exclusion criteria does not apply to patients crossing-over from MBG453 arm to the combination MBG453 + azacitidine arm, unless MBG453 was ceased due to MBG453-related toxicity.
– Patients with active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur should not be excluded
– History of or current drug-induced interstitial lung disease or pneumonitis grade greater than or equal to 2
– Subject has been diagnosed with another malignancy, unless disease-free for at least 2 years and not needing active treatment. Patients with fully excised BCC/SCC/CIN or other minor malignancy are not excluded
– Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation
– Use of any live vaccines against infectious diseases (i.e. Influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment
– Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade greater than or equal to 2) with an LVEF of less than 40%, uncontrolled hypertension or clinically significant arrhythmia
• Acute myocardial infarction or unstable angina pectoris less than 3 months prior to study entry
– Known hypersensitivity to azacitidine or mannitol.
Dr. Carolyn Grove
Australasian Leukaemia & Lymphoma Group
Phase 1 / Phase 2