A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological Malignancies (BEXMAB)
Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Macrophages, Immunotherapy, Hematological, CLEVER-1, bexmarilimab, hematological neoplasms, azacitidine, venetoclax, myeloid cells
Eligibility Criteria
Inclusion Criteria:
Patient ≥ 18 years of age who presents with one of the following conditions:
- Morphologically confirmed diagnosis of MDS with revised International Prognostic Scoring System (rIPSS) risk categories: intermediate, high and very high.
- Morphologically confirmed diagnosis of CMML-2 with indication for azacitidine treatment.
- CMML and MDS patient with response failure to HMA or therapy regimen including HMA.
- Morphologically confirmed diagnosis of r/r AML following at least 1 line of prior therapies with indication for azacitidine treatment.
- Morphologically confirmed diagnosis of AML in patients unfit for induction therapy with indication for azacitidine-venetoclax treatment.
- Leukocyte count < 20 x10^9/L (< 25 x10^9/L for newly diagnosed AML). Hydroxycarbamide use is permitted to meet this criterion in MDS and AML but not in CMML.
- Adequate renal function.
- Adequate liver function.
Exclusion Criteria:
- Patient with acute promyelocytic leukemia (APL) or myeloproliferative CMML as defined by leukocyte count > 13 x10^9/L.
- Eastern Cooperative Oncology Group (ECOG) performance status >2 (except newly diagnosed AML where ECOG 3 is allowed for patients < 75 years).
- Allogeneic transplantation less than 6 months prior screening.
- Patient with active auto-immune disorder (except type I diabetes, celiac disease, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia).
- The patient requires systemic corticosteroid (≥10 mg/day prednisone or equivalent) or other immunosuppressive treatment.
- Less than 21 days since the last dose of intravenous anticancer chemotherapy or less than 14 days or five half-lives (whichever is shorter) from a small molecule targeted therapy or oral anticancer chemotherapy before the first study treatment.
- Any immunotherapy or investigational therapy within preceding 28 days from the first study treatment.
- Pregnant or lactating women.
- History of chronic ulcers or clinically relevant liver disease leading to Child Pugh Score C or higher.
Sites / Locations
- City of Hope National Medical CenterRecruiting
- University of Texas, MD Anderson Cancer CenterRecruiting
- Helsinki University HospitalRecruiting
- Kuopio University HospitalRecruiting
- Oulu University HospitalRecruiting
- Tampere University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Phase 1 - Intermediate/high risk MDS, CMML 10-19%, MDS/CMML failure to HMA, r/r AML
Phase 1 - Newly diagnosed AML patients non-fit for induction therapy
Phase 2 - Intermediate/high risk MDS, CMML, MDS/CMML failure to HMA, r/r AML & newly diagnosed AML
Standard of care azacitidine as per label; bexmarilimab 4 dose levels at once every week (Q1W) followed by once every 2 weeks (Q2W); 28-day cycle
Standard of care azacitidine and venetoclax as per label; bexmarilimab 4 dose levels Q1W followed by Q2W; 28-day cycle
Standard of care venetoclax and/or azacitidine as per label plus bexmarilmab