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

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia (AML)
• Interventions: Drug: Siltuximab

• Registration Number: NCT05697510
• Lead Sponsor: Nantes University Hospital

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.

Study Timeline

• Study First Submitted: 2023-01-11
• Study First Submitted QC: 2023-01-24
• Study First Posted: 2023-01-26
• Study Start: 2023-03-16
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-04
• Last Update Posted: 2023-04-06
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
SILTUXIMAB	Siltuximab	-

Primary Outcome Measures

Name	Time	Method
number of DLT	45 days

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CHU de Nantes; 🇫🇷 Nantes, France