Clinical trial NCT05697510: Dose-escalation of Siltuximab in Combination With Idarubicin and Cytarabine Chemotherapy in Patients With Acute Myeloblastic Leukaemia (AML) With Poor Prognosis: SILTUXILAM
Official title: Monocentric Phase 1 Study With Dose-escalation of Siltuximab in Combination With Idarubicin and Cytarabine Chemotherapy in Patients With Acute Myeloblastic Leukaemia (AML) With Poor Prognosis: SILTUXILAM
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: AML IL-6 SILTUXIMAB
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2023-01-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase 1 dose escalation study testing the addition of an anti-IL6 (siltuximab) to standard induction chemotherapy for high-risk AML.

Detailed description: Administration of siltuximab at day 8 of induction following a classical induction using idarubicin 8mg/m2/d for 5 days and cytarabine 100mg/m2/d for 7 days.

Eligibility criteria: Inclusion Criteria:

* age \>= 18 years
* AML with a poor prognosis defined according to the criteria below:

LAM First line: Age \<60 years and unfavorable risk according to the 2017 ELN Age\> = 60 years old and intermediate or unfavorable risk according to the ELN 2017 LAM in Relapse: whatever the age

* ECOG \<= 2
* Patient eligible for intensive chemotherapy
* Informed consent
* Liver function tests: transaminases \<3x normal, bilirubin \<1.5X normal
* Creatinine clearance\> 60ml / min
* LVEF\> = 50%

Exclusion Criteria:

* Patients with FLT3 ITD or TKD mutation eligible for FLT3 inhibitor therapy
* Uncontrolled infection
* Hep B, C, HIV +
* History of diverticulosis / diverticulitis
* Patients at high risk of gastrointestinal perforation
* No social security or any other scheme
* Pregnant women or patient unable to take contraception (pill, abstinence, IUD not allowed) in case of fertility. contraceptive pill, abstinence, unauthorised IUD) in case of fertility. A patient who cannot continue contraception for at least 3 months after the last SILTUXIMAB injection is not eligible for inclusion.
* Lactating women
* Minors
* Adults under guardianship, curatorship or legal protection
* Hypersensitivity to one of the active substances or to one of the excipients

Primary outcomes:
measure: number of DLT
timeFrame: 45 days
Secondary outcomes:
measure: Evaluation of the response to induction therapy with idarubicin + cytarabine + siltuximab
timeFrame: Day 30 and Day 45
measure: Evaluation of response at D15 after induction
timeFrame: Day 15
measure: Assessment of myelotoxicity
timeFrame: Day 45
measure: Overall survival
timeFrame: Month 6
measure: Leukaemia-free survival
timeFrame: Month 6
measure: Event-free survival
timeFrame: Month 6
measure: Incidence of relapse if remission
timeFrame: Month 6
measure: Infections
timeFrame: Month 6
measure: Cytokine levels: FLT3L and IL-6
timeFrame: Day 1, Day 8, Day 15, Day 22
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU de Nantes
Study officials:
References: