A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological Malignancies
Acute Myeloid LeukemiaChronic Myelomonocytic LeukemiaMyelodysplastic SyndromesRelapsed/Refractory AML
Investigational drug(s) / intervention(s)
BexmarilimabAzacitidineVenetoclax
Bexmarilimab: Intravenous
Azacitidine: As per label, subcutaneous
Venetoclax: Oral
Study summary
This is a study to assess the safety of increasing dose levels of bexmarilimab when combined with standard of care (SoC) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML); Phase 1 aims to identify the recommended phase 2 dose (RP2D) of bexmarilimab based on safety, tolerability and pharmacological activity; Phase 2 will investigate the preliminary efficacy of the combination treatment in selected indications from Phase 1.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Reporting of incidence and frequency of dose limiting toxicities (DLTs). — From study start to end of Cycle 1 (each cycle is 28 days)
Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and serious adverse events (SAE). — From study start to 30 days after end of treatment (EOT)
Complete response (CR) rate for MDS and CMML-2. — From study start to 30 days after EOT
Overall response rate (ORR) for MDS and CMML failure to prior HMA. — From study start to 30 days after EOT
Complete remission with incomplete blood recovery (CRi) for r/r AML. — From study start to 30 days after EOT
Minimal residual disease (MRD) status for newly diagnosed AML. — From study start to 30 days after EOT
Trial sites (10)
Facility
City
Region
Status
City of Hope National Medical Center
Duarte
California
Yale Cancer Center
New Haven
Connecticut
UNC Lineberger Comprehensive Cancer Center
Chapel Hill
North Carolina
University of Texas, MD Anderson Cancer Center
Houston
Texas
Helsinki University Hospital
Helsinki
Finland
Kuopio University Hospital
Kuopio
Finland
Oulu University Hospital
Oulu
Finland
Tampere University Hospital
Tampere
Finland
The Christie NHS Foundation Trust
Manchester
United Kingdom
Royal Cornwall Hospitals NHS Trust
Truro
United Kingdom
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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