Clinical trial NCT05749276: 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)
Official title: Multicentric Phase 1 Study With 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Adult Patients With Adverse Risk Acute Myeloblastic Leukemia
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2023-03-01
Enrollment: 12
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Continual Reassessment Method for MTD
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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%.

Exclusion Criteria:

* 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

Primary outcomes:
measure: DLT
timeFrame: DAY 45
Secondary outcomes:
measure: response to the induction treatment
timeFrame: DAY 45
measure: Assessment of myelotoxicity
timeFrame: Day 1
measure: Overall survival (OS)
timeFrame: 6 months
measure: Event-free survival (EFS)
timeFrame: 6 months
measure: Relapse incidence
timeFrame: 6 months
measure: Flow cytometry (FCM) investigation of myeloid-derived suppressor cells
timeFrame: Day 45
measure: Comparison of MDSC values in CMF
timeFrame: Day 45
measure: research on the level of CD38 expression on blasts
timeFrame: Day 1
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital, Angers
name: MATHILDE HUNAULT
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Rennes
name: MARC BERNARD
role: PRINCIPAL_INVESTIGATOR
References: