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)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- DLT
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 60 ans
- •Poor prognosis AML defined according to the following criteria:
- •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%.
排除标准
- •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
- •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
研究组 & 干预措施
Darzalex
DARZALEX®
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)
干预措施: Darzalex (Drug)
结局指标
主要结局
DLT
时间窗: DAY 45
Dose at which no toxic effect is observed, by determination of the LDT (Toxic Limit Dose). A TLD is defined by the occurrence of grade ≥ 3 daratumumab related toxicity that is not reversible after 7 days (except for haematological toxicity) or the absence of emergence from aplasia at D45 of induction (in the absence of treatment failure). Toxicity is assessed according to NCI-CTCAE version 5 criteria. The search for DLT is continued until D45 of induction.
次要结局
- Relapse incidence(6 months)
- research on the level of CD38 expression on blasts(Day 1)
- Comparison of MDSC values in CMF(Day 45)
- Flow cytometry (FCM) investigation of myeloid-derived suppressor cells(Day 45)
- Assessment of myelotoxicity(Day 1)
- Event-free survival (EFS)(6 months)
- response to the induction treatment(DAY 45)
- Overall survival (OS)(6 months)