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

Ludwig Maximilian University of Munich

Status and phase

Enrolling

Phase 2

Conditions

Acute Myeloid Leukemia

Treatments

Drug: Relatlimab

Drug: Nivolumab

Drug: Azacitidine Injection

Study type

Interventional

Funder types

Other

Identifiers

NCT04913922

CA224-065

Details and patient eligibility

About

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).

Enrollment

30 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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