Dose-escalation of Siltuximab in Combination With Idarubicin and Cytarabine Chemotherapy in Patients With Acute Myeloblastic Leukaemia (AML) With Poor Prognosis: SILTUXILAM

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Acute Myeloid Leukemia (AML)

Intervention / Treatment
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* Drug: Siltuximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SILTUXIMAB<br> | Drug: Siltuximab<br>* Administration of siltuximab at day 8 of induction following a classical induction; 3 dose levels : 7, 9 and 11mg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of DLT |  | 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the response to induction therapy with idarubicin + cytarabine + siltuximab | Calculation of complete remission (CR) and CR with incomplete recovery (CRi) according to the ELN 2017 definition | Day 30 and Day 45 | 
| Evaluation of response at D15 after induction | percent bone marrow blasts at D15 (myelogram) | Day 15 | 
| Assessment of myelotoxicity | Neutrophil recovery time (>1.0 × 109/L) from D1; Platelet recovery time (>100 × 109/L) from D1 | Day 45 | 
| Overall survival | delay from D1 of induction to date of last news or death | Month 6 | 
| Leukaemia-free survival | delay between the date of CR and the date of relapse or death or the date of the last follow-up | Month 6 | 
| Event-free survival | delay between D1 of induction and the date of relapse, death or date of last | Month 6 | 
| Incidence of relapse if remission | relapse rate at last follow-up | Month 6 | 
| Infections | monitoring of AEs infection | Month 6 | 
| Cytokine levels: FLT3L and IL-6 | Cytokine levels: FLT3L and IL-6 | Day 1, Day 8, Day 15, Day 22 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML IL-6 SILTUXIMAB