Escalation of Doses of Daratumumab in Combination With Chemotherapy (Idarubicin and Cytarabine or CPX-351) in Patients of 60 Years Old or More With Adverse Risk Acute Myeloblastic Leukemia (AML) (DARALAM)

Официальное название

Multicentric Phase 1 Study With Escalation of Doses of Daratumumab in Combination With Chemotherapy (Idarubicin and Cytarabine or CPX-351) in Patients of 60 Years Old or More With Adverse Risk Acute Myeloblastic Leukemia (AML) (DARALAM)

Обзор

To search for a Maximum Tolerated Dose (MTD) for the combination of daratumumab and induction chemotherapy with Idarubicin and cytarabine or CPX-351 in patients with Acute Myeloblastic Leukemia (AML) of poor prognosis

Вмешательства

• Препарат Darzalex
  DARZALEX® = Daratumumab. Solution for injection, 1800 mg/15 mL, single vial. Sub-cutaneous administration. * Dose level 1 : 1800 mg Day 1 * Dose level 2 : 1800 mg Day 1 and 8 (+/- 2 days) * Dose level 3 : 1800 mg à Day 1, 8 (+/- 2 days) and D15 (+/- 2 days)

Первичные конечные точки

• DLT [Срок оценки: DAY 45]

Вторичные конечные точки (8)

• response to the induction treatment [Срок оценки: DAY 45]
• Assessment of myelotoxicity [Срок оценки: Day 1]
• Overall survival (OS) [Срок оценки: 6 months]
• Event-free survival (EFS) [Срок оценки: 6 months]
• Relapse incidence [Срок оценки: 6 months]
• Flow cytometry (FCM) investigation of myeloid-derived suppressor cells [Срок оценки: Day 45]
• Comparison of MDSC values in CMF [Срок оценки: Day 45]
• research on the level of CD38 expression on blasts [Срок оценки: Day 1]

Критерии участия

Критерии включения

• Age >= 60 ans
• Poor prognosis AML defined according to the following criteria:1. For first-line AML:intermediate or unfavorable risk according to ELN 2022 2.for Relapsed AML:regardless of the ELN risk group
• ECOG <= 2
• Patient eligible for intensive chemotherapy
• Who provide their written informed consent
• Liver workup: transaminases < 3x normal, bilirubin < 1.5 X normal
• Creatinine clearance > 60ml/mn
• LVEF >= 50%.

Критерии исключения

• Patients with FLT3 ITD or TKD mutation
• Patients with tuberculosis
• Patients with documented active infection with COVID 19
• Patients with hereditary fructose intolerance (HFI)
• Uncontrolled infection
• Active or past infection with Hep B, C or HIV+
• Not Affiliated with French social security system or no beneficiary from such system
• Pregnant women or patients who cannot take contraception ( contraceptive pill, abstinence, unauthorised IUD) in case of fertility. A patient who cannot continue contraception for at least 6 months after the last injection of DARATUMUMAB is not eligible for inclusion.
• Breastfeeding women
• Minors
• Adults under guardianship, curatorship or safeguard of justice
• Hypersensitivity to any of the active ingredients or excipients
• Patients with significant cardiovascular pathology including any of the following: myocardial infarction within 6 months prior to study entry, unstabilized coronary artery disease, uncontrolled hypertension, congestive heart failure.
• Patient with disease requiring systemic immunosuppressive therapy (such as high-dose steroids defined as ≥ 10mg prednisone or equivalent per day) within 4 weeks prior to the 1st scheduled dose of study treatment with the exception of dermocorticoids

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• CHU de Nantes — Nantes

Идентификаторы

NCT: NCT05749276 · RC22_0372

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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