Acute Myeloid Leukemia Clinical Trial
Official title:
Phase I/II Open-Label Study to Assess Safety, Tolerability and Preliminary Efficacy of the CLEVER-1 Antibody Bexmarilimab in Combination With Azacitidine or Azacitidine/Venetoclax in Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia or Acute Myeloid Leukemia
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.
Status | Recruiting |
Enrollment | 181 |
Est. completion date | December 31, 2024 |
Est. primary completion date | December 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Finland | Helsinki University Hospital | Helsinki | |
Finland | Kuopio University Hospital | Kuopio | |
Finland | Oulu University Hospital | Oulu | |
Finland | Tampere University Hospital | Tampere | |
United States | Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina |
United States | City of Hope National Medical Center | Duarte | California |
United States | University of Texas, MD Anderson Cancer Center | Houston | Texas |
United States | Yale Cancer Center | New Haven | Connecticut |
Lead Sponsor | Collaborator |
---|---|
Faron Pharmaceuticals Ltd |
United States, Finland,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Reporting of incidence and frequency of dose limiting toxicities (DLTs). | From study start to end of Cycle 1 (each cycle is 28 days) | ||
Primary | 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) | ||
Primary | Complete response (CR) rate for MDS and CMML-2. | From study start to 30 days after EOT | ||
Primary | Overall response rate (ORR) for MDS and CMML failure to prior HMA. | From study start to 30 days after EOT | ||
Primary | Complete remission with incomplete blood recovery (CRi) for r/r AML. | From study start to 30 days after EOT | ||
Primary | Minimal residual disease (MRD) status for newly diagnosed AML. | From study start to 30 days after EOT | ||
Secondary | Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs. | From study start to 30 days after EOT | ||
Secondary | Clinical efficacy measures based on progression free survival analyses defined as the time from study start to the date of documented disease progression or death from any cause, whichever occurs first, up to 2 years. | 24 months from study start | ||
Secondary | Clinical efficacy measures based on overall survival analyses defined as the length measured from study start to death from any cause up to 2 years. | 24 months from study start | ||
Secondary | Anti-bexmarilimab antibody positivity occurrence rate pre-dose and at defined timepoints during treatment. | 24 months from study start | ||
Secondary | Serum concentrations of bexmarilimab at defined timepoints pre-dose and post-dose of single and repeat bexmarilimab administrations using peripheral blood. | From study start to end of Cycle 2 (each cycle is 28 days) |
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