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

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

ClinicalTrials.gov Identifier: NCT04623216

Novartis Reference Number: CMBG453F12201

Last Update: Mar 31, 2022

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

The primary purpose of this study is to test the hypothesis that preemptive treatment with sabatolimab, alone or in combination with azacitidine, when administered to participants with AML/secondary AML who are in complete remission with positive measurable residual disease post-allogeneic hematopoietic stem cell transplantation (MRD+ post-aHSCT), can 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

Condition

Acute Myeloid Leukemia

Phase

Phase 1

Phase 2

Overall status

Recruiting

Start date

Sep 14, 2021

Completion date

Nov 03, 2026

Gender

All

Age(s)

12 Years - 99 Years (Child, Adult, Older Adult)

Interventions

Biological

Sabatolimab

Sabatolimab is a solution in vial for IV infusion

Drug

Azacitidine

Azacitidine comes in Vial for IV infusion or subcutaneous administration

Eligibility Criteria

Inclusion Criteria:

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.
Diagnosis of AML/secondary AML and received one prior aHSCT performed to control AML
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.
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%.

Exclusion Criteria:

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.
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

Other protocol defined inclusion/exclusion criteria may apply