None listed
Conditions
Brief summary
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). Who is it for? You may be eligible for to receive this treatment if you are a part of the AMLM26 Intercept trial which is registered on ANZCTR with ID ACTRN12621000439842 (ie if you are aged 18 or older, you have been diagnosed with progressive acute myeloid leukemia, and are currently in your first or second morphologic remission with a known and trackable minimal residual disease (MRD) marker.). If you are on the AMLM26 Intercept trial you may be eligible for this treatment option if your minimal residual disease (very small amounts of disease) is rising. The trial management committee will review your disease characteristics and determine your best treatment option(s) available on the trial. Study details Participants who choose to enrol in this study may be randomly allocated by chance (similar to flipping a coin), to receive either MBG453 alone or MBG453 with azacitidine or another available treatment option within the Intercept platform which the TMC has indicated are your best treatment options. MBG453 is given intravenously by itself (treatment A) or in combination with azacitidine therapy administered either intravenously or subcutaneously (injections under the skin, Treatment B). Participants who receive Treatment A will have MBG453 administered as a single 800mg intravenous dose on day 1 of a 28 day treatment cycle for 12 cycles. Participants who receive Treatment B will have daily 75mg doses of azacitidine during the first week of a 28 day treatment cycle and 800mg of MBG453 on day 8. This treatment will also continue for 12 cycles. After 100 days on therapy, participants in Treatment A who are not responding to the single therapy may be re-allocated to Treatment B for another 12 cycles (after rescreening for eligibility). Participants will undergo a disease assessment at screening after cycle 1, cycle 3, cycle 6 and then 3 monthly until progression. This will require blood tests and bone marrow biopsies. Safety and tolerability of treatment will be assessed throughout the trial whilst you are receiving treatment. Health related quality of life during treatment will be assessed on the first treatment day of 3 consecutive cycles. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that MBG453 will be well tolerated and may improve outcomes for future patients, however, there may be no clear benefit from participation in this study.
Interventions
The ALLG AMLM26 INTERCEPT trial is an adaptive trial allowing the testing of multiple new therapeutic options targeting various AML biomarkers in a staged manner. The Master Protocol outlines the overall study structure (this is detailed in ANZCTR entry ACTRN12621000439842). There will be separate domains for each AML biomarker being investigated. Each domain will have at least one investigational agent. Each investigational agent may be used on its own and/or in combination with other agents. Each option will be a different treatment arm within a domain. Separate Therapy-Specific Protocol Appendices will include treatment-specific information for each investigational agent including all of the treatment arms specific to that investigational agent. Each treatment arm may be targeted to a specific AML biomarker (domain) and/or may be used when patients have no targetable option available. This entry is for the investigational agent MBG453. This will have 2 treatment arms - arm A MBG453 alone and arm B MBG453 in combination with azacitidine. Eligible patients will be randomly allocated to one of the two treatment arms. MBG453 will be administered via intravenous infusion over 30minutes or up to 2hrs if clinically indicated. Treatment arm A - MBG453 on its own will be given at a dose of 800mg on day 1 of a 28 day cycle by intravenous infusion. Treatment arm B - MBG453 and azacitidine. Azacitidine 75mg/m2 days 1-7, MBG453 800mg on day 8 by intravenous infusion. Azacitidine will be given subcutaneously (sc) or intravenously (IV) for 7 days from days 1-7 or using the 5-2-2 schedule (administered for 5 consecutive days on days 1-5, followed by a two-day break, then administered for two consecutive days on days 8-9), with MBG453 infusion on day 8 out of a 28-day cycle. Whether azacitidine is given via IT or SC is per the hospital's standard clinical practice. Both treatment arms will be given for 12 cycles. Patients will attend hospital to receive treatment. If there is poor compliance with protocol procedures patients may be removed from the trial. If patients have not responded to treatment within 100days of commencing MBG453 alone patients will be able to crossover to receive MBG453 + Azacitidine, if they undergo screening procedures and meet eligibility to go onto this combined treatment arm.
Sponsors
Australasian Leukaemia & Lymphoma Group
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Meets inclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol including: a. Master Protocol Inclusion Criteria. b. the mutation/mutations specified for this treatment arm in Master Protocol 2. Meets MRD eligibility for INTERCEPT therapy based on a screening sample taken no more than 42 days prior to cycle 1 of day 1 of treatment on this treatment arm. Eligibility will be confirmed by the MRD review committee. 3. ECOG0-2 4. 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) 5. 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 6. 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) 7. Agrees to follow the recommended contraception procedures for this treatment domain
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: 1. Presence of any general exclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol 2. 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 3. Subject is HIV positive 4. Patients with greater than or equal to 5% myeloblasts in bone marrow on morphologic assessment 5. 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. 6. 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. 7. 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. 8. 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 9. History of or current drug-induced interstitial lung disease or pneumonitis grade greater than or equal to 2 10. 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 11. Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation 12. Use of any live vaccines against infectious diseases (i.e. Influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment 13. 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 14. Known hypersensitivity to azacitidine or mannitol.
Outcome results
None listed