AMLM26/T5 INTERCEPT
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).
Key inclusion criteria
Patient must meet eligibility to come onto the Intercept Master Protocol (as detailed in linked entry ACTRN12621000439842).
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.
– ECOG0-2
– 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 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.
– ECOG0-2
– 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient must meet eligibility to come onto the Intercept Master Protocol (as detailed in linked entry ACTRN12621000439842).
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.
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.
Louise Hay
louise.hay@health.wa.gov.au
08 6383 3207
Dr. Carolyn Grove
Australasian Leukaemia & Lymphoma Group
Phase 1 / Phase 2
AMLM26/T5 INTERCEPT
ACTRN12621001265864