Subjects with Acute myeloid leukemia MedDRA version: 20.0 Level: LLT Classification code 10001941 Term: AML System Organ Class: 100000004864
Conditions
Interventions
Product Name: Relatlimab
Product Code: BMS-986016
Pharmaceutical Form: Concentrate for dispersion for infusion
INN or Proposed INN: Relatlimab
Current Sponsor code: BMS-986016
Concentration unit: mg/m
Sponsors
Klinikum der Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort 1 (R/R AML): • Patients with AML who have failed first line therapy (other than hydroxyurea) or patients who have relapsed after achieving a CR, CRp, or CRi. • Patients with AML who have failed up to one prior salvage therapy (i.e. salvage 1 or 2 status) will also be eligible. Allogeneic stem cell transplant for patients in remission at the time of transplant will not be considered a salvage regimen. Hydroxyurea if used alone will not be considered a salvage regimen. Cohort 2 (frontline older AML): • Patients aged =65 years with previously untreated AML who are unfit for or decline standard induction therapy. • Prior therapy with hydroxyurea, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed, however, prior therapy with chemotherapy agents for the disease under study is not allowed. All Cohorts: • Age =18 years • Eastern Cooperative Oncology Group (ECOG) Performance Status =2 • Adequate organ function • Patients must provide written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: • Patients with APL. • Patients with known allergy or hypersensitivity to nivolumab, 5-azacytidine, relatlimab, or any of their components. • Patients with a history of life-threatening toxicity related to prior immune therapy (e.g. anti- CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T cell costimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (e.g., hormone replacement after endocrinopathy). • Patients who have previously been treated with immunotherapeutic drugs targeting PD-1/PD-L1 in combination with 5-azacytidine. • Patients who have previously been treated with LAG-3 targeted agents. • Patients with a known history of severe interstitial lung disease or severe pneumonitis. • Patients with an active, known or suspected history of any autoimmune disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Lead-in-phase: Maximum tolerated dose and dose-limiting toxicities of relatlimab in combination with nivolumab and 5-azacytidine in patients with R/R AML Expansion phase: • Objective response rate to treatment with relatlimab + nivolumab + 5- azacytidine in patients with R/R AML • ORR to treatment with relatlimab + nivolumab + 5- azacytidine in older patients (=65 years) with newly diagnosed AML;Secondary Objective: • % of grade I/II and grade III/IV toxicities for patients with R/R AML on therapy with relatlimab + nivolumab + 5- azacytidine • % of grade I/II and grade III/IV toxicities for older patients with newly diagnosed AML on therapy with relatlimab + nivolumab + 5-azacytidin • Number of patients with R/R AML who achieve a HI in platelets, hemoglobin, or ANC on therapy with relatlimab + nivolumab + 5-azacytidine • Number of patients with R/R AML who achieve =50% reduction in blasts on therapy with relatlimab + nivolumab + 5-azacytidine. • Number of older patients with newly diagnosed AML who achieve an HI in platelets, hemoglobin, or ANC on therapy with relatlimab + nivolumab + 5-azacytidine • Number of older patients with newly diagnosed AML who achieve =50% reduction in blasts on therapy with relatlimab + nivolumab + 5-azacytidine • Duration of response, DFS, and OS of patients with R/R AML treated with relatlimab + nivolumab + 5-azacytidine;Primary end point(s): Lead-in phase: MTD and DLT of relatlimab in combination with nivolumab and 5-azacytidine in patients with R/R AML Expansion phase: ORR to treatment with relatlimab + nivolumab + 5-azacytidine in patients with R/R AML Expansion phase: ORR to treatment with relatlimab + nivolumab + 5-azacytidine in older patients (=65 years) with newly diagnosed AML ;Timepoint(s) of evaluation of this end point: Lead-in phase: after completion of 1st cycle of treatment and evaluation of DLTs in 6-12 patients (number of subjects depending on DLT occurrence) Expansion phase: after completion of study ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To determine the safety of therapy with relatlimab + nivolumab + 5-azacytidine for patients with R/R AML • To determine the safety of therapy with relatlimab + nivolumab + 5-azacytidine for older patients with newly diagnosed AML • To determine the number of patients with R/R AML who achieve a hematologic improvement (HI) in platelets, hemoglobin, or absolute neutrophil count (ANC) and the number of patients with R/R AML who achieve =50% reduction in blasts on therapy with relatlimab + nivolumab + 5-azacytidine. • To determine the number of older patients with newly diagnosed AML who achieve an HI in platelets, hemoglobin, or ANC and the number of older patients with newly diagnosed AML who achieve =50% reduction in blasts on therapy with relatlimab + nivolumab + 5-azacytidine. • To assess the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with R/R AML treated with relatlimab + nivolumab + 5-azacytidine. • To assess the duration of response, DFS, and OS in older patients with newly diagnosed AML treated with relatlimab + nivolumab + 5-azacytidine. ;Timepoint(s) of evaluation of this end point: after completion of study (30 patients) | — |
Countries
Germany, United States
Contacts
Public ContactTranslational Cancer Immunotherapy
Klinikum der Universität München
Outcome results
None listed