Escalation of Doses of Daratumumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients of 60 Years Old or More With Adverse Risk Acute Myeloblastic Leukemia (AML) (DARALAM)
- Conditions
- Adult Patients With Adverse Risk Acute Myeloblastic Leukemia
- Interventions
- Registration Number
- NCT05749276
- Lead Sponsor
- Nantes University Hospital
- Brief Summary
To search for a Maximum Tolerated Dose (MTD) for the combination of daratumumab and induction chemotherapy with Idarubicin and cytarabine in patients with Acute Myeloblastic Leukemia (AML) of poor prognosis
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 12
- 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%.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Darzalex 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)
- Primary Outcome Measures
Name Time Method DLT 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.
- Secondary Outcome Measures
Name Time Method Comparison of MDSC values in CMF Day 45 Flow cytometry (FCM) investigation of myeloid-derived suppressor cells Day 45 Assessment of myelotoxicity Day 1 Neutrophil recovery time (\>1.0 × 109/L) from D1 - Recovery time of platelets (\>100 × 109/L) from D1
Event-free survival (EFS) 6 months time from D1 of induction to date of relapse, death or date of last
Relapse incidence 6 months response to the induction treatment DAY 45 calculation of the rate of complete remission (CR) with negative residual disease (CR MRD-), CR, CR with incomplete haematological recovery (CRi), MLFS (morphological leukemia free state), partial response (PR) or treatment failure according to the 2022 NLE definition between D30 and D45.
Overall survival (OS) 6 months time from D1 of induction to date of last contact or death
research on the level of CD38 expression on blasts Day 1