Relatlimab With Nivolumab and 5-Azacytidine for the Treatment of AML

• Status: Recruiting
• Trial end date: 2026-03-31
• Target enrollment: 0
• Participant gender: All

Summary

The clinical trial will test the safety and tolerability of a combination therapy (azacitidine in combination with two checkpoint inhibitors, nivolumab [Anti-PD1] and relatlimab [Anti-LAG3]) in patients with relapsed/refractory Acute Myeloid Leukemia (AML) and patients ≥ 65 years with initial diagnosis of AML.

Primary objectives are:

• maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the combination therapy during the lead-in phase of the clinical trial (6-12 patients) and

• objective response rate (ORR) of the combination therapy in the phase II part of the study (up to 24 patients).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ludwig-Maximilians - University of Munich
• Treatments: Azacitidine; Nivolumab

Criteria

Inclusion Criteria:

Cohort 1 (R/R AML):

• Patients with AML who have failed first line induction chemotherapy (consisting of a minimum of two intensive chemotherapy cycles, e.g. 7+3 or HAM) or patients with AML who have relapsed after achieving complete remission (CR), CRi, or CRp, or patients who have failed up to one prior salvage therapy

Cohort 2 (frontline older AML):

• Patients aged ≥65 years with previously untreated AML who are unfit for or decline standard induction therapy.

General inclusion criteria:

• Patients not eligible for intensive induction chemotherapy and/or allogeneic stem cell transplant.

• Age ≥18 years

• ECOG Performance Status ≤2

• Adequate organ function:

Total bilirubin ≤2 x ULN (≤3 × ULN if due to leukemic involvement or Gilbert's syndrome) AST and ALT ≤2.5 × ULN (≤5.0 × ULN if due to leukemic involvement) Serum creatinine ≤2 × ULN or glomerular filtration rate (GFR) ≥50 mL/h

• Adequate cardiac function: TTE with documented LVEF ≥50%

• At least 2 weeks OR at least 5 half-lives interval from prior treatment to time of initiation of study medication

• GvHD of grade ≤A on ≤10 mg prednisone without any additional immunosuppressive therapies (tacrolimus, ciclosporin, etc.)

• Written informed consent

• Negative pregnancy test and adequate methods of contraception for females of childbearing potential, adequate methods of contraception for males

Exclusion Criteria:

• Acute promyelocytic leukemia (APL)

• Biphenotypic or bilineage leukemia

• Known allergy or hypersensitivity to 5-azacytidine, nivolumab, relatlimab, or any of their components

• History of life-threatening toxicity related to prior immune therapy

• Previous treatment with immunotherapeutic drugs targeting PD-1/PD-L1 in combination with 5-azacytidine

• Previous treatment with LAG-3 targeted agents

• Known history of severe interstitial lung disease or severe pneumonitis

• Known history (active, known, or suspected) of any of the following autoimmune diseases:

inflammatory bowel disease rheumatoid arthritis systemic progressive sclerosis systemic lupus erythematosus autoimmune vasculitis

• Active uncontrolled pneumonitis

• Active uncontrolled infection

• Symptomatic or poorly controlled CNS leukemia

• Confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent

• Uncontrolled or significant cardiovascular disease

• Troponin T (TnT) or I (TnI) > 2 × institutional ULN

• Organ allografts

• Allogeneic hematopoietic stem cell transplantation within the last 100 days before first study drug administration

• Active GvHD > grade A

• Known human immunodeficiency virus seropositivity

• Known positivity for hepatitis B by surface antigen expression or active hepatitis C infection

• Other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety

• Patients unwilling or unable to comply with the protocol

• Patients who are pregnant or breastfeeding

• Prisoners and subjects who are compulsory detained