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

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Siltuximab

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 Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: MARION GAUTIER; Phone Number: +33253526204; Email: marion.gautier@chu-nantes.fr

Study Locations

• France
  • Nantes, France, 44093
    • Recruiting
    • CHU de Nantes
    • Contact: Pierre PETERLIN; Phone Number: +33240083271; Email: pierre.peterlin@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2023
• Primary Completion (Anticipated): June 30, 2025
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: AML IL-6 SILTUXIMAB
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Antineoplastic Agents; Siltuximab
• Other Study ID Numbers: RC22_0233; 2022-501171-14-00 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No