Monocentric Phase 1 Study With Escalation of Doses of Tocilizumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients With Acute Myeloblastic Leukemia (AML)

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

Detailed Description
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Administration of tocilizumab 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.

Official Title
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Monocentric Phase 1 Study With Escalation of Doses of Tocilizumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients With Acute Myeloblastic Leukemia (AML) With Poor Prognosis: TOCILAM

Conditions
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Acute Myeloid Leukemia (AML)

Intervention / Treatment
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* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - 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: Uncontrolled infection Hep B, C, HIV + History of diverticulosis / diverticulitis No social security or any other scheme Pregnant women or patient unable to take contraception(contraceptive pill, abstinence, IUD unauthorized) in case of fertility. A patient who cannot continue contraception for at least 3 months after the last injection of TOCILIZUMAB is not eligible. Lactating women Minors Adults under guardianship, curatorship or legal protection Hypersensitivity to one of the active substances or to one of the excipients Patients with tuberculosis Patients documented with active COVID

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Continual Reassessment Method for MTD
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tocilizumab|Administration of tocilizumab at day 8 of induction following a classical induction|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of DLT |  | 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of response |  | 25 months | 
| Percentage of medullary blaste |  | 24 months | 
| number of days of neutrophil recovery |  | 30 months | 
| number of days of platelets recovery |  | 30 months | 
| Number of death |  | 30 months | 
| number of days between remission and relapse |  | 30 months | 
| number of days between remission and death |  | 30 months | 
| number of days between remission and last follow-up date |  | 30 months | 
| number of days between Day 1 and last follow-up date |  | 30 months | 
| number of days between Day 1 and death |  | 30 months | 
| number of days between Day 1 and relapse |  | 30 months | 
| number of relapse |  | 30 months | 
| Number of cytokine |  | 25 months | 
| Number of tocilizumab |  | 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML il-6 tocilizumab