Acute Myeloid Leukemia (AML)
Conditions
Keywords
AML IL-6 SILTUXIMAB
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.
Interventions
DRUGSiltuximab
Administration of siltuximab at day 8 of induction following a classical induction; 3 dose levels : 7, 9 and 11mg/kg
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| number of DLT | 45 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France
Contacts
Primary ContactMARION GAUTIER
Outcome results
None listed