A phase ll multi-center, single arm, safety and efficacy study of MBG453 in combination with azacitidine and venetoclax for the treatment of Acute Myeloid Leukemia (AML) in adult patients unfit for chemotherapy

JRCT ID: jRCT2021210050

Registered date:19/11/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: AML
• Date of first enrollment: 01/11/2021
• Target sample size: 4
• Countries of recruitment: France,Japan,Italy,Japan,Taiwan,Japan,Australia,Japan,US,Japan,Canada,Japan,Korea,Japan,Germany,Japan,Spain,Japan
• Study type: Interventional

Intervention(s)

Drug: MBG453
Solution for intravenous infusion
Other Name: Sabatolimab

Drug: Venetoclax
Tablet for oral administration

Drug: Azacitidine
Solution for subcutaneous injection or intravenous infusion

Outcome(s)

Primary Outcome

1.Incidence of dose limiting toxicities (Safety run-in patients only) [ Time Frame: From Cycle 1 Day 8 to end of Cycle 2; Cycle =28 Days ]
Assessment of tolerability of MBG in combination with venetoclax and azacitidine
2.Percentage of subjects achieving complete remission (CR) [ Time Frame: at least 6 cycles from last patient first treatment up to 100 weeks (each cycle =28 Days) ]
Assessing Complete Remission (CR) Rate (Safety run in (expansion dose Level only) + Expansion)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Signed informed consent must be obtained prior to participation in the study.
2.Age >= 18 years at the date of signing the informed consent form (ICF)
3.Newly diagnosed with AML (based on WHO 2016 classification (Arber et al 2016), who are not suitable for intensive chemotherapy based on one or more of the following criteria:
- age >= 75 years
- ECOG performance status of 2 or 3
- or at least one of the following comorbidities:
- severe cardiac comorbidity (including congestive heart failure requiring treatment, ejection =< 50%, or chronic stable angina)
- pulmonary comorbidity (including DLCO =< 65% or FEV1 =< 65%)
- moderate hepatic impairment with total bilirubin > 1.5 to 3 times the upper limit of normal
- eGFR >= 30 mL/min/1.73 m2 to < 45 mL/min/1.73 m2 (estimation based on Modification of Diet in Renal Disease (MDRD) formula, by local laboratory)
- any other comorbidity (to be documented in the CRF) that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Novartis Medical Monitor before study enrollment.
4.Not planned for hematopoietic stem-cell transplantation (HSCT)
5.Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3

Exclude criteria

1.Prior exposure to TIM-3 directed therapy
2.History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, venetoclax or MGB453) or monoclonal antibodies (mAbs) and/or their excipients
3.Current use or use within 14 days prior to randomization of systemic, steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion are allowed and not considered a form of systemic treatment.
4.Previous treatment at any time, with any of the following antineoplastic agents, approved or investigational; checkpoint inhibitors, venetoclax and hypomethylating agents (HMAs) such as decitabine or azacitidine.
5.Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).
6.Live vaccine administered within 30 Days prior to randomization

Related Information

• Primary Sponsor: Hirano Takamitsu
• Secondary ID(s): NCT04150029