Sabatolimab as a Treatment for Patients With Acute Myeloid Leukemia and Presence of Measurable Residual Disease After Allogeneic Stem Cell Transplantation.

Recruitment & Eligibility

Status: Active, not recruiting

Sex: All

Target Recruitment: 24

Inclusion Criteria

Inclusion Criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. At the date of signing the informed consent form (ICF), eligible participants must be = 18 years for the adult cohorts; and = 12 years old but < 18 years old for the adolescent cohort (cohort 5), which will open after completion of Safety Run-in. 3. Diagnosis of AML/secondary AML and received one prior aHSCT performed to control AML 4. Participants in complete remission (< 5% bone marrow blasts, absence of circulating blasts, and absence of extramedullary disease) with measurable residual disease (MRD) positivity by local assessment, at any time between day 100 and day 365 after allogeneic stem cell transplantation. 5. Ability to provide a fresh bone marrow aspirate sample collected within 28 days from enrollment/randomization, and immediately shipped to a Novartis designated central laboratory for MRD testing. 6. Systemic GvHD (graft versus host disease) prophylaxis or treatment [immunosuppressive treatment (IST)] completely tapered for at least two weeks prior to study entry. Prednisone dose = 5 mg/day or equivalent corticosteroid dose is allowed. 7. Participants who are found with MRD positivity while still on or tapering systemic GvHD prophylaxis or treatment, MRD positivity must be re-confirmed at least 2 week after the last dose of IST 8. For the adult cohorts, participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. For the adolescent cohort, participants must have a Karnofsky (age = 16 years) or Lansky (age < 16 years) performance status score = 50%. Exclusion Criteria: 1. Prior exposure to TIM-3 directed therapy at anytime. 2. History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients 3. Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Participants whose disease is controlled under antiviral therapy should not be excluded. 4. Active acute GvHD grade III-IV according to standard criteria (Harris 2016). 5. Active moderate chronic GvHD of the lungs according to NIH consensus criteria. Active severe chronic GvHD according to NIH consensus criteria. 6. History of another primary malignancy that is currently clinically significant or currently requires active intervention. 7. Any concurrent severe and/or active uncontrolled infection requiring parenteral antibacterial, antiviral or antifungal therapy (such as severe pneumonia, meningitis, or septicemia) 8. Active autoimmune disease requiring systemic therapy (e.g. corticosteroids). Topical, inhaled, nasal and ophthalmic steroids are not prohibited. Replacement corticosteroids therapy is allowed and not considered a form of systemic treatment 9. Live vaccine administered within 30 days prior to the first day of study treatment (Cycle 1 Day 1) 10. Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes mellitus, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) or history of serious organ dysfunction or disease involving the heart, kidney, or liver Other protocol defined inclusion/exclusion criteria may apply

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities (Safety Run-in in adult cohorts 1 and 2 only);Percentage of adult subjects with absence of hematologic relapse per Investigator assessment (Safety Run-in and Expansion);Incidence of dose limiting toxicities (Safety confirmation in adolescent cohort 5 only)

Secondary Outcome Measures

Name	Time	Method
Incidence of grade III or IV acute Graft versus Host Disease (aGvHD);Incidence of moderate to severe Chronic GVHD (cGvHD);Peak of Serum Concentration (Cmax) sabatolimab;Trough serum concentration (Cmin) sabatolimab;Anti-drug antibody (ADA) prevalence on-treatment;ADA prevalence at baseline;Time from start of treatment to the date of first documented GvHD- free/ relapse- free survival;Time from start of treatment to the date of first documented hematologic relapse or death due to any cause, whichever occurs first;Incidence of grade 3 immune-related adverse events not attributed to GvHD;Percentage of participants with measurable residual disease (MRD) positive at baseline who become MRD negative

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