Clinical trial NCT04547062: Monocentric Phase 1 Study With Escalation of Doses of Tocilizumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients With Acute Myeloblastic Leukemia (AML)
Official title: 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"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Keywords: AML il-6 tocilizumab
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2020-09-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Continual Reassessment Method for MTD
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: number of DLT
timeFrame: 45 days
Secondary outcomes:
measure: Number of response
timeFrame: 25 months
measure: Percentage of medullary blaste
timeFrame: 24 months
measure: number of days of neutrophil recovery
timeFrame: 30 months
measure: number of days of platelets recovery
timeFrame: 30 months
measure: Number of death
timeFrame: 30 months
measure: number of days between remission and relapse
timeFrame: 30 months
measure: number of days between remission and death
timeFrame: 30 months
measure: number of days between remission and last follow-up date
timeFrame: 30 months
measure: number of days between Day 1 and last follow-up date
timeFrame: 30 months
measure: number of days between Day 1 and death
timeFrame: 30 months
measure: number of days between Day 1 and relapse
timeFrame: 30 months
measure: number of relapse
timeFrame: 30 months
measure: Number of cytokine
timeFrame: 25 months
measure: Number of tocilizumab
timeFrame: 25 months
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU of Nantes
Study officials:
References: