A Phase 2 Study of Gemtuzumab Ozogamicin (GO)-Gilteritinib Combination in Adults With FLT3-ITD and/or FLT3-TKD Relapse/Refractory (R/R) AML

NCT05199051 | Active Not Recruiting Phase 2

• 3 other identifiers: 2020/652023-504176-25-002021-001813-35
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 12

Brief Summary

This is a national, open-label, single-arm, multicenter phase II trial evaluating the safety and efficacy of adding gilteritinib, a new FLT3 inhibitor to the AGORA platform, consisting of the combination of an intermediate dose of cytarabine and a divided dose of GO in adult patients with R / R AML with an FLT3-ITD and/or FLT3-TKD mutation.

Conditions

AML; Leukaemia (Acute Myeloid)

Keywords

AML; Gemtuzumab Ozogamicin Gilteritinib Combination; relapse; refractory; Leukaemia

Outcome Measures

Primary Outcomes (2)

• Stage 1 - Safety of the addition of gilteritinib to the AGORA treatment platform

  The primary objective of the first stage is to evaluate the safety of combining gilteritinib with the Gemtuzumab Ozogamicin (GO) -cytarabine AGORA platform in patients with FLT3-ITD and/or FLT3-TKD mutated Relapse/Refractory (R/R) Acute Myeloïd Leukemia (AML), through occurrence of dose-limiting toxicity (DLT).

  18 months

• Stage 2 - Event-free survival (EFS)

  The primary objective of the second extension stage is to evaluate the efficacy of combining gilteritinib with the Gemtuzumab Ozogamicin (GO)-cytarabine AGORA platform in patients with FLT3-ITD and/or FLT3-TKD mutated Relapse/Refractory (R/R) Acute Myeloïd Leukemia (AML) through event-free survival (EFS).

  60 months

Secondary Outcomes (14)

• Response rates to the study treatment

  60 months

• Early mortality rates, at day-30

  30 months

• Incidence of subsequent allogeneic Hematopoietic Stem Cell Transplantation (HSCT) overall.

  60 months

• Incidence of subsequent allogeneic Hematopoietic Stem Cell Transplantation in responding patients specifically.

  60 months

• Evaluation of Duration of response (DOR) of treatment

  60 months

Study Arms (1)

Gemtuzumab ozogamicine - Cytarabine - Gilteritinib

EXPERIMENTAL

For Gemtuzumab ozogamicine administrated during the induction phase at D1, D4 and D7, 3mg/m2/day (5mg max), IV, 2h of infusion. For Cytarabine during induction and consolidation phase at D1 to D5, 1000 mg/m2, IV, 2h of infusion. For Gilteritinib during induction phase from D10 for 14 consecutive days, per os, two doses level study with dose level 1 (80mg/d) in part 1 or dose level 2 (80 or 120mg/d depending of the result of part 1) in part 2. During consolidation (2 cycles max) from D8 for 14 consecutive days, per os, 120mg/d or reduced dose of 80 mg/kg is planned to be used in patients receiving concomitantly CYP3A4 inhibitors. During the maintenance (24 months max) dose level 2 (120mg/d), per os.

Combination Product: Gemtuzumab ozogamicine - Cytarabine - Gilteritinib

Interventions

Gemtuzumab ozogamicine - Cytarabine - Gilteritinib COMBINATION_PRODUCT

See Arms description paragraph

Also known as: Mylotarg - Aracytine - Xospata

Gemtuzumab ozogamicine - Cytarabine - Gilteritinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 years old or more
• Confirmed diagnosis of R/R AML positive for CD33 antigen as determined locally by immunophenotyping according to routine practice, defined as:
• AML refractory to 1 or 2 intensive chemotherapy courses or a treatment by hypomethylating agents (HMAs)
• Or AML in first hematologic relapse or progression after front-line therapy, including intensive chemotherapy or hypomethylating agents (HMAs).
• Previous treatments with FLT3 inhibitors (other than gilteritinib) are allowed
• R/R AML secondary to a prior chemotherapy or radiotherapy for another cancer (tAML) could be included.
• Presence of a FLT3-ITD mutation (allelic ratio ≥0.05 at last evaluation)\* or a FLT3 TKD mutation
• Patient with no contraindication to gemtuzumab ozogamicin (GO), cytarabine and gilteritinib
• ECOG performance status ≤2
• AST and ALT ≤ 2.5 x upper the limit of normal (ULN) and/or total and direct serum bilirubin ≤ 1.5 x ULN unless considered due to leukemia
• Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the formula usually used by the investigator
• Written informed consent obtained prior to any screening procedures
• Eligible for National Health Insurance in France

You may not qualify if:

• Acute promyelocytic leukemia or AML with BCR-ABL1 gene fusion
• Secondary AML (sAML) defined by a history of prior myelodysplastic syndrome (MDS) or myeloproliferative syndrome (MPN) including chronic myelomonocytic leukemia (CMML)
• Patient with contraindications to the administration of gemtuzumab ozogamicin (GO), cytarabine and gilteritinib. Refer to the SPCs of the molecules mentioned concerning the contraindications, special warnings, precautions for use, dose modifications in the event of toxicity, contraception and monitoring of patients and drugs prohibited or to be used with caution.
• Proven central nervous system leukemic involvement
• Prior allogeneic HSCT within the last 6 months and/or history of acute GVHD of grade \>1
• Prior treatment with gemtuzumab ozogamicin within the last 3 months preceding the initiation of the treatment in the present clinical trial
• Uncontrolled or active malignant disease within prior 12 months (excluding cutaneous basal cell carcinoma, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised)
• Uncontrolled or significant cardiovascular history or symptoms including:
• Prior anthracycline exposure equivalent to more than 550 mg/m2 of daunorubicin
• History of clinically relevant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation or torsade de pointes)
• History of 2° (Mobitz II) or 3° heart block (subjects with pacemakers are allowed if they have no history of clinically relevant arrhythmias with the pacemaker)
• History of uncontrolled angina pectoris or MI within 6 months
• History of NYHA Class 3 or 4 heart failure
• Left ventricular ejection fraction ≤ 50% or less than the institutional lower limit of normal
• History of complete left bundle branch block

Sponsors & Collaborators

• Centre Antoine Lacassagne: lead
• Astellas Pharma Inc: collaborator
• Pfizer: collaborator
• Acute Leukemia French Association: collaborator

Study Sites (12)

CHU d'Amiens

Amiens, France

Location

CHU d'Angers

Angers, France

Location

CHU Bordeaux

Bordeaux, France

Location

CHU de Caen

Caen, France

Location

CHMS de Chambery

Chambéry, France

Location

HIA Percy

Clamart, France

Location

CHU Limoges

Limoges, France

Location

CHRU Nancy

Nancy, France

Location

Centre Hospitalier Universitaire de Nice

Nice, France

Location

Hôpital Saint Louis

Paris, France

Location

Centre Henri Becquerel

Rouen, France

Location

Centre Hospitalier de Versailles

Versailles, France

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Juliette LAMBERT, MD-PHD

  Versailles Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2021
• First Posted: January 20, 2022
• Study Start: June 3, 2023
• Primary Completion (Estimated): July 10, 2028
• Study Completion (Estimated): July 10, 2028
• Last Updated: January 5, 2026

Record last verified: 2025-12

Locations

FR (12)