A study of Cusatuzumab in combination with a standard treatment in patients with newly diagnosed AML who are not eligible for intensive chemotherapy
Zusammenfassung der Studie
This is a multicenter phase 2 study in which both you and your study doctor know which group you are randomly assigned to in order to evaluate the efficacy, safety, and effects of Venetoclax/Azacitidine/Cusatuzumab (VAC) compared to Venetoclax/Azacitidine (VA) in patients with newly diagnosed acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy. The study is being conducted in Europe and North America, with approximately 120 patients randomly assigned. The enrolled participants will be randomly assigned in a 2:1 ratio to treatment with VAC or VA. The study participant group includes individuals at higher risk for adverse events according to the VA-specific risk model from the University of Colorado, enrolling participants with unfavorable, intermediate, and favorable risk in a 3:1:1 ratio. Several tests for blood and bone marrow analysis will be performed. Cycles will continue every 28 days indefinitely until the disease progresses, an alternative treatment line (including HSCT) is initiated, unacceptable toxicity occurs, the investigator or participant decides to discontinue, or death occurs. The safety of Cusatuzumab will be assessed through physical examinations, clinical laboratory tests, electrocardiograms (ECGs), and monitoring of adverse events (AEs). An independent data monitoring committee (DMC) will be established to ensure the ongoing safety of individuals participating in this study, review the futility and final analyses, and to review the ongoing study objectives.
(BASEC)
Untersuchte Intervention
Enrolled participants will then be randomly assigned in a 2:1 ratio to each treatment with VAC or VA (i.e., 48 participants with unfavorable risk, 16 participants with intermediate risk, and 16 participants with favorable risk will receive VAC and 24 participants with unfavorable risk, 8 participants with intermediate risk, and 8 participants with favorable risk will receive VA).
(BASEC)
Untersuchte Krankheit(en)
Acute myeloid leukemia (AML) is a malignant blood disorder characterized by infiltration of the bone marrow, blood, and other tissues by cells that are abnormally formed by the blood cell formation system (Arber et al., 2016). AML is diagnosed in the USA in 20,000 new patients per year, and approximately 11,000 patients in the USA die each year. The 5-year survival rate for adult patients diagnosed with AML is about 30%. However, the outlook varies widely and depends on treatment, age, other illnesses, and the biological features of AML. For most young and fit patients, treatment typically consists of intensive chemotherapy followed by a stem cell transplant (HSCT). With this strategy, the 5-year overall survival (OS) is about 50%. In a group of young and fit patients with specific genetic features of AML, the majority of patients can be cured with intensive chemotherapy alone. For older patients or those with other illnesses that exclude these aggressive approaches, the B-cell lymphoma-2 (BCL-2) inhibitor Venetoclax in combination with an agent (HMA) such as Azacitidine is a current standard therapy. Response rates of approximately 66% have been reported for these combinations; however, 33% do not respond, and the median overall survival is only about 12 to 14 months (DiNardo et al., 2020). For these patients who do not respond well to Venetoclax plus Azacitidine (VA), treatment options remain limited (Bruserud et al, 2017). Based on these observations, new treatment approaches for individuals with AML who cannot tolerate intensive chemotherapy remain an important therapeutic goal.
(BASEC)
- Diagnosis of AML (acute myeloid leukemia) - Previously untreated AML, except for emergency leukapheresis, hydroxyurea, and/or 1 dose of 1 to 2 g/m2 cytarabine prior to study initiation to control hyperleukocytosis. - Considered unsuitable for intensive chemotherapy if at least one of the following criteria is met: a. The participant is ≥ 75 years old and has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 OR b. The participant is ≥ 18 to 74 years old and has one of the following comorbidities: (1) ECOG performance status of 2 or 3 (2) Cardiac status with, among others, one of the following: treatment-requiring heart failure or ejection fraction ≤ 50% or chronic stable angina (3) Known presence of a diffusion capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in one second (FEV1) ≤ 65% (4) Creatinine clearance (CrCl) ≥ 15 mL/min to < 45 mL/min (5) Liver dysfunction with total bilirubin > 1.5 to 3 × the upper limit of normal (ULN) (6) Another comorbidity that the investigators believe is incompatible with conventional intensive chemotherapy. (BASEC)
Ausschlusskriterien
- Any prior treatment for AML or a myelodysplastic syndrome (MDS) (except for the treatments listed in the inclusion criterion: "Previously untreated AML, except for emergency leukapheresis, hydroxyurea, and/or 1 dose of 1 to 2 g/m2 cytarabine prior to study initiation to control hyperleukocytosis."). - The participant has received an HMA for MDS or a myeloproliferative neoplasm. - Leukemic involvement in the central nervous system. (BASEC)
Studienstandort
Bern, Freiburg, St Gallen
(BASEC)
Sponsor
Jens Lachmann ICON Clinical Research (Switzerland) GmbH c/o Experfina AG,Picassoplatz 8 4052 Basel Jens.Lachmann@iconplc.com +41 79 593 4489
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Prof. Dr. Thomas Pabst
+41 31 632 41 14
studies@clutterinsel.chISNELSPITAL, Universitätsspital Bern Universitätsklinik für Medizinische Onkologie Klinische Forschungseinheit C.L Lory-Haus EG. Raum 25 Freiburgstrasse 41 3010 Bern
(BASEC)
Wissenschaftliche Auskünfte
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Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
23.09.2024
(BASEC)
ICTRP Studien-ID
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Offizieller Titel (Genehmigt von der Ethikkommission)
A multicenter, open-label, randomized, phase 2 study of venetoclax and azacitidine plus cusatuzumab versus venetoclax and azacitidine alone in newly diagnosed AML patients who are not candidates for intensive therapy (BASEC)
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Untersuchte Krankheit(en)
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