Acute Myeloid LeukemiaPhase 1/2NCT04623216
Sabatolimab as a Treatment for Patients With Acute Myeloid Leukemia and Presence of Measurable Residual Disease After Allogeneic Stem Cell Transplantation.
A Phase 1/2 study testing Sabatolimab and Azacitidine in people with Acute Myeloid Leukemia, run by Novartis Pharmaceuticals at 9 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 99 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Sabatolimab and Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 14 Sep 2021to 22 Aug 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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%.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
Italy4 sites
Novartis Investigative Site
Bergamo, BG, 24127
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Brescia, BS, 25123
Novartis Investigative Site
Roma, RM, 00165
Germany3 sites
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Münster, 48149
About this study
Official title: A Phase Ib/II, Open Label Study of Sabatolimab as a Treatment for Patients With Acute Myeloid Leukemia and Presence of Measurable Residual Disease After Allogeneic Stem Cell Transplantation
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
Read the detailed description
This is a phase Ib/II, open label, multi-center study of sabatolimab as monotherapy and in combination with azacitidine, in participants with AML/secondary AML who had received one aHSCT and achieved complete remission but MRD+, by local assessment, anytime at >= Day 60 after aHSCT and at least 2 weeks after immunosuppressive medications had been tapered off.
The study was planned to enroll approximately 59 participants and be conducted in two parts:
Part 1 was a Safety Run-in of approximately 20 participants, to assess whether sabatolimab as monotherapy at the two tested dose levels (400 mg and 800 mg intravenously Q4W) was safe when administered in the post-aHSCT setting. For each dose level, once the required number of evaluable participants had been confirmed, enrollment would be halted until participants had completed the dose limiting toxicities (DLT) observation period (≥ 8 weeks following the first dose). Following the observation period for DLTs, a Safety Review Meeting was to be conducted after each dose level to assess safety and determine the recommended dose for expansion to proceed with enrollment of additional cohorts in Part 2 of the study.
Part 2 consisted of sabatolimab monotherapy expansion cohort of approximately 13 participants, sabatolimab in combination with azacitidine cohort of approximately 20 participants, and an adolescent cohort of approximately 6 participants (≥ 12 years but < 18 years of age) with sabatolimab as monotherapy. Sabatolimab was to be administered at the recommended dose for expansion determined in Part 1.
After initiating Part 2, Novartis took the decision to put enrollment in permanent halt and terminate the sabatolimab program. This decision was not driven by any safety concerns.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Sabatolimab, Azacitidine
- 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
- Medical subject headings
- Leukemia, Myeloid, Acute, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SabatolimabBiological
Also called MBG453
Sabatolimab is a solution in vial for IV infusion
AzacitidineDrug
Azacitidine comes in Vial for IV infusion or subcutaneous administration
| Study group | Role | What they receive |
|---|---|---|
| Sabatolimab 400mg | Experimental | Safety cohort 1: Participants in this arm will receive sabatolimab 400mg intravenously every 4 weeks. Receives: Biological: Sabatolimab |
| Sabatolimab 800mg | Experimental | Safety cohort 2: Participants in this arm will receive sabatolimab 800mg intravenously every 4 weeks. Receives: 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. Receives: Biological: Sabatolimab; Drug: Azacitidine |
| Sabatolimab | Experimental | Expansion cohort 4: Participants in this arm will receive sabatolimab at the recommended dose for expansion. Receives: 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. Receives: Biological: Sabatolimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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)
Assessment of the treatment emergent grade III or IV aGvHD. Acute GvHD: Grade IV acute GvHD, Stage ≥3 lower GI acute GvHD (consistent with Grade III acute GvHD) or Stage ≥3 liver acute GvHD (consistent with Grade III GvHD).
Measured: From start of treatment to up to 36 months from last patient first treatment.
Incidence of Moderate to Severe Chronic GVHD (cGvHD)
Assessment of the treatment emergent moderate or severe cGvHD. Chronic GvHD: Moderate chronic GvHD of the lungs, Severe chronic GvHD.
Measured: From start of treatment to up to 36 months from last patient first treatment.
Peak of Serum Concentration (Cmax) Sabatolimab
Cmax is the maximal serum concentration of sabatolimab.
Measured: 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
Cmin is the concentration of sabatolimab prior to next dosing or after end of treatment.
Measured: 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)
Time from start of treatment to the date of first documented occurrence or worsening of treatment emergent grade III or IV aGvHD or moderate to severe cGvHD requiring initiation of systemic treatment, morphologic/hematologic relapse, or death due to any cause, whichever occurs first
Measured: From start of treatment to up to 36 months from last patient first treatment
Relapse-free Survival (RFS)
Time from start of treatment to the date of first documented hematologic relapse or death due to any cause, whichever occurs first.
Measured: From start of treatment to up to 36 months from last patient first treatment
Percentage of Participants With Measurable Residual Disease (MRD) Positive at Baseline Who Become MRD Negative
Percentage of participants with centrally confirmed MRD+ status at baseline converting to MRD- within the first 6 cycles of study treatment.
Measured: From start of treatment until end of Cycle 6 (Cycle = 28 Days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2020
- Study start14 Sep 2021
- Primary completion22 Aug 2024
- Study completion22 Aug 2024
Why it stopped: Study was stopped following a strategic decision from the Sponsor. It was not based on any safety findings or safety concerns with sabatolimab.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04623216
- Sponsor's protocol ID
- CMBG453F12201
- Other IDs
- 2020-000869-17
- Status last verified
- Oct 2025
- First submitted
- 3 Nov 2020
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.