Relatlimab With Nivolumab and 5-Azacytidine for the Treatment of AML
An Open-Label Phase II Study of Relatlimab (BMS-986016) With Nivolumab (BMS-936558) in Combination With 5-Azacytidine for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia and Newly Diagnosed Older Acute Myeloid Leukemia Patients
Ludwig-Maximilians - University of Munich
30 participants
May 5, 2021
INTERVENTIONAL
Conditions
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).
Eligibility
Inclusion Criteria14
- 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.
- 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 Criteria24
- 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
Interventions
s.c. 75 mg/m2 BSA for 7 days
480 mg i.v.
80-160mg i.v.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04913922