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

Sponsor
Nantes University Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05697510
Collaborator
(none)
12
1
1
28.9
0.4

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

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Feb 1, 2023
Anticipated Primary Completion Date :
Jun 30, 2025
Anticipated Study Completion Date :
Jun 30, 2025

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

  1. number of DLT [45 days]

Secondary Outcome Measures

  1. 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

  2. Evaluation of response at D15 after induction [Day 15]

    percent bone marrow blasts at D15 (myelogram)

  3. Assessment of myelotoxicity [Day 45]

    Neutrophil recovery time (>1.0 × 109/L) from D1; Platelet recovery time (>100 × 109/L) from D1

  4. Overall survival [Month 6]

    delay from D1 of induction to date of last news or death

  5. 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

  6. Event-free survival [Month 6]

    delay between D1 of induction and the date of relapse, death or date of last

  7. Incidence of relapse if remission [Month 6]

    relapse rate at last follow-up

  8. Infections [Month 6]

    monitoring of AEs infection

  9. Cytokine levels: FLT3L and IL-6 [Day 1, Day 8, Day 15, Day 22]

    Cytokine levels: FLT3L and IL-6

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 99 Years
Sexes Eligible for Study:
All
Accepts 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

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.
Responsible Party:
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT05697510
Other Study ID Numbers:
  • RC22_0233
  • 2022-501171-14-00
First Posted:
Jan 26, 2023
Last Update Posted:
Jan 26, 2023
Last Verified:
Jan 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Nantes University Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 26, 2023