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

NCT04623216 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CMBG453F122012020-000869-17
• Study Type: interventional
• Target: 24
• Locations: 4 countries
• Sites: 9

Brief Summary

The primary purpose of this study was to test the hypothesis that preemptive treatment with sabatolimab, alone or in combination with azacitidine, when administered to participants with Acute myeloid leukemia (AML)/secondary AML who were in complete remission with positive measurable residual disease post-allogeneic hematopoietic stem cell transplantation (Minimal residual disease (MRD)+ post- Allogeneic hematopoietic stem cell transplantation (aHSCT)), could enhance the graft versus leukemia (GvL) response and prevent or delay hematologic relapse without an unacceptable level of treatment-emergent toxicities, including clinically significant acute and/or chronic graft-versus-host disease (GvHD) and immune-related adverse events

Conditions

Acute Myeloid Leukemia

Keywords

Sabatolimab; MBG453; TIM-3; Azacitidine; Acute Myeloid Leukemia; AML; Allogeneic Hematopoietic Stem Cell Transplantation; aHSCT; Measurable Residual Disease; MRD; Phase Ib/II; Acute myeloid leukemia Hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (3)

• Rate of Dose Limiting Toxicities (Safety Run-in in Adult Sabatolimab 400mg & 800mg Only)

  Assessment of tolerability of sabatolimab in adults and adolescents in the post allogenic stem cell transplantation setting. This was determined by the number of participants with at least one event - All grades. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor that occurs during the DLT observation period and meets the severity criteria as per protocol.

  From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days

• Percentage of Adult Subjects With Absence of Hematologic Relapse Per Investigator Assessment (Safety Run-in and Expansion)

  The percentage of adult participants for whom no evidence of hematologic relapse (no evidence of bone marrow blasts ≥5%, no evidence of reappearance of blasts in the blood; no evidence of development of extramedullary disease) has been documented after 6 cycles of study treatment or earlier discontinuation at the recommended dose of sabatolimab 800 mg.

  From Cycle 1 Day 1 to end of Cycle 6; Cycle = 28 Days

• Rate of Dose Limiting Toxicities (Safety Confirmation in Adolescent Cohort Only)

  Assessment of tolerability of sabatolimab in adolescent participants in the post allogeneic stem cell transplantation setting. This was determined by the number of participants with at least one event - All grades. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor that occurs during the DLT observation period and meets the severity criteria as per protocol.

  From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days

Secondary Outcomes (7)

• Incidence of Grade III or IV Acute Graft Versus Host Disease (aGvHD)

  From start of treatment to up to 36 months from last patient first treatment.

• Incidence of Moderate to Severe Chronic GVHD (cGvHD)

  From start of treatment to up to 36 months from last patient first treatment.

• Peak of Serum Concentration (Cmax) Sabatolimab

  Cycle 1 Day 5 (end of infusion) and Cycle 3 Day 1 or Day 5 (end of infusion) and Cycle 24 Day 1 (end of infusion); Cycle =28 Days

• Trough Serum Concentration of (Cmin) Sabatolimab

  Adult cohorts: Pre-dose on Day 1 (safety run-in) or Day 5 (expansion) of Cycle 1, 3, 6 and 24 (safety run-in only); Adolescent cohort: Pre-dose on Day 1 of Cycle 1, 2, 3 and 6; Cycle = 28 Days

• Graft Versus Host Disease (GvHD)-Free/Relapse-free Survival (GRFS)

  From start of treatment to up to 36 months from last patient first treatment

Study Arms (5)

Sabatolimab 400mg

EXPERIMENTAL

Safety cohort 1: Participants in this arm will receive sabatolimab 400mg intravenously every 4 weeks.

Biological: Sabatolimab

Sabatolimab 800mg

EXPERIMENTAL

Safety cohort 2: Participants in this arm will receive sabatolimab 800mg intravenously every 4 weeks.

Biological: Sabatolimab

Sabatolimab + Azacitidine

EXPERIMENTAL

Expansion cohort 3: Participants in this arm will receive sabatolimab at the recommended dose for expansion in combination with azacitidine.

Biological: Sabatolimab; Drug: Azacitidine

Sabatolimab

EXPERIMENTAL

Expansion cohort 4: Participants in this arm will receive sabatolimab at the recommended dose for expansion.

Biological: Sabatolimab

Sabatolimab (adolescent cohort)

EXPERIMENTAL

Adolescent safety cohort (cohort 5): ≥12 to \< 18 year old adolescent participants in this arm will receive sabatolimab at the recommended dose for expansion.

Biological: Sabatolimab

Interventions

Sabatolimab BIOLOGICAL

Sabatolimab is a solution in vial for IV infusion

Also known as: MBG453

Sabatolimab; Sabatolimab (adolescent cohort); Sabatolimab + Azacitidine; Sabatolimab 400mg; Sabatolimab 800mg

Azacitidine DRUG

Azacitidine comes in Vial for IV infusion or subcutaneous administration

Sabatolimab + Azacitidine

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study.
• 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.
• Participants in complete remission (\< 5% bone marrow blasts, absence of circulating blasts, and absence of extramedullary disease) with MRD positivity by local assessment or by central assessment where required (e.g., USA sites), any time at ≥ Day 60 after aHSCT
• Diagnosis of AML/secondary AML and received one prior aHSCT performed to control AML
• 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.
• 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.
• 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
• 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%.

You may not qualify if:

• Prior exposure to TIM-3 directed therapy at anytime.
• History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients
• Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Participants whose disease is controlled under antiviral therapy should not be excluded.
• Active acute GvHD grade III-IV according to standard criteria (Harris 2016).
• Active moderate chronic GvHD of the lungs according to NIH consensus criteria. Active severe chronic GvHD according to NIH consensus criteria.
• History of another primary malignancy that is currently clinically significant or currently requires active intervention. Participants who are receiving adjuvant therapy, such as hormone therapy, are eligible
• Any concurrent severe and/or active uncontrolled infection requiring parenteral antibacterial, antiviral or antifungal therapy (such as severe pneumonia, meningitis, or septicemia)
• 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
• Live vaccine administered within 30 days prior to the first day of study treatment (Cycle 1 Day 1)
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Bergamo, BG, 24127, Italy

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Brescia, BS, 25123, Italy

Location

Novartis Investigative Site

Roma, RM, 00165, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasm, Residual

Interventions

sabatolimab; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novatis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 10, 2020
• Study Start: September 14, 2021
• Primary Completion: August 22, 2024
• Study Completion: August 22, 2024
• Last Updated: October 16, 2025
• Results First Posted: June 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

IT (4); DE (3); ES (1); FR (1)