Dose-escalation of Siltuximab in Combination With Idarubicin and Cytarabine Chemotherapy in Patients With Acute Myeloblastic Leukaemia (AML) With Poor Prognosis: SILTUXILAM
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
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 Design
Arms and Interventions
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
|
Outcome Measures
Primary Outcome Measures
- number of DLT [45 days]
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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age >= 18 years
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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
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ECOG <= 2
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Patient eligible for intensive chemotherapy
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Informed consent
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Liver function tests: transaminases <3x normal, bilirubin <1.5X normal
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Creatinine clearance> 60ml / min
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LVEF> = 50%
Exclusion Criteria:
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Patients with FLT3 ITD or TKD mutation eligible for FLT3 inhibitor therapy
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Uncontrolled infection
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Hep B, C, HIV +
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History of diverticulosis / diverticulitis
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Patients at high risk of gastrointestinal perforation
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No social security or any other scheme
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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.
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Lactating women
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Minors
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Adults under guardianship, curatorship or legal protection
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Hypersensitivity to one of the active substances or to one of the excipients
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | CHU de Nantes | Nantes | France | 44093 |
Sponsors and Collaborators
- Nantes University Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RC22_0233
- 2022-501171-14-00