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

Acute Myeloid Leukemia (AML) Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05697510
• Other study ID #: RC22_0233
• Secondary ID: 2022-501171-14-0
• Status: Recruiting
• Phase: Phase 1
• Start date: March 16, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2023
• Source: Nantes University Hospital
• Contact: MARION GAUTIER
• Phone: +33253526204
• Email: marion.gautier[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Siltuximab
Administration of siltuximab at day 8 of induction following a classical induction; 3 dose levels : 7, 9 and 11mg/kg

Locations

Country	Name	City	State
France	CHU de Nantes	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of DLT		45 days
Secondary	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
Secondary	Evaluation of response at D15 after induction	percent bone marrow blasts at D15 (myelogram)	Day 15
Secondary	Assessment of myelotoxicity	Neutrophil recovery time (>1.0 × 109/L) from D1; Platelet recovery time (>100 × 109/L) from D1	Day 45
Secondary	Overall survival	delay from D1 of induction to date of last news or death	Month 6
Secondary	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
Secondary	Event-free survival	delay between D1 of induction and the date of relapse, death or date of last	Month 6
Secondary	Incidence of relapse if remission	relapse rate at last follow-up	Month 6
Secondary	Infections	monitoring of AEs infection	Month 6
Secondary	Cytokine levels: FLT3L and IL-6	Cytokine levels: FLT3L and IL-6	Day 1, Day 8, Day 15, Day 22