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

Primary Purpose

Acute Myeloid Leukemia (AML)

Status
Recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Siltuximab
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring AML IL-6 SILTUXIMAB

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU de NantesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SILTUXIMAB

Arm Description

Outcomes

Primary Outcome Measures

number of DLT

Secondary Outcome Measures

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
Evaluation of response at D15 after induction
percent bone marrow blasts at D15 (myelogram)
Assessment of myelotoxicity
Neutrophil recovery time (>1.0 × 109/L) from D1; Platelet recovery time (>100 × 109/L) from D1
Overall survival
delay from D1 of induction to date of last news or death
Leukaemia-free survival
delay between the date of CR and the date of relapse or death or the date of the last follow-up
Event-free survival
delay between D1 of induction and the date of relapse, death or date of last
Incidence of relapse if remission
relapse rate at last follow-up
Infections
monitoring of AEs infection
Cytokine levels: FLT3L and IL-6
Cytokine levels: FLT3L and IL-6

Full Information

First Posted
January 11, 2023
Last Updated
April 4, 2023
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05697510
Brief Title
Dose-escalation of Siltuximab in Combination With Idarubicin and Cytarabine Chemotherapy in Patients With Acute Myeloblastic Leukaemia (AML) With Poor Prognosis: SILTUXILAM
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 16, 2023 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
AML IL-6 SILTUXIMAB

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SILTUXIMAB
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Siltuximab
Intervention Description
Administration of siltuximab at day 8 of induction following a classical induction; 3 dose levels : 7, 9 and 11mg/kg
Primary Outcome Measure Information:
Title
number of DLT
Time Frame
45 days
Secondary Outcome Measure Information:
Title
Evaluation of the response to induction therapy with idarubicin + cytarabine + siltuximab
Description
Calculation of complete remission (CR) and CR with incomplete recovery (CRi) according to the ELN 2017 definition
Time Frame
Day 30 and Day 45
Title
Evaluation of response at D15 after induction
Description
percent bone marrow blasts at D15 (myelogram)
Time Frame
Day 15
Title
Assessment of myelotoxicity
Description
Neutrophil recovery time (>1.0 × 109/L) from D1; Platelet recovery time (>100 × 109/L) from D1
Time Frame
Day 45
Title
Overall survival
Description
delay from D1 of induction to date of last news or death
Time Frame
Month 6
Title
Leukaemia-free survival
Description
delay between the date of CR and the date of relapse or death or the date of the last follow-up
Time Frame
Month 6
Title
Event-free survival
Description
delay between D1 of induction and the date of relapse, death or date of last
Time Frame
Month 6
Title
Incidence of relapse if remission
Description
relapse rate at last follow-up
Time Frame
Month 6
Title
Infections
Description
monitoring of AEs infection
Time Frame
Month 6
Title
Cytokine levels: FLT3L and IL-6
Description
Cytokine levels: FLT3L and IL-6
Time Frame
Day 1, Day 8, Day 15, Day 22

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
MARION GAUTIER
Phone
+33253526204
Email
marion.gautier@chu-nantes.fr
Facility Information:
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre PETERLIN
Phone
+33240083271
Email
pierre.peterlin@chu-nantes.fr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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