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FLT3-ITD Targeted Therapy in Fit AML Patients

ConditionAML (Acute Myeloid Leukemia)
Trial statusNot yet recruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18-75
SponsorEuropean Organisation for Research and Treatment of Cancer - EORTC

About this trial

This international, multicenter, randomized (1:1), open-label phase II/III trial will evaluate the efficacy and safety of gilteritinib combined with azacitidine and venetoclax (experimental arm) versus standard "7+3" induction plus a FLT3inhibitor (quizartinib or midostaurin) (control arm) in newly diagnosed FLT3-ITD mutated AML patients eligible for intensive chemotherapy.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Newly diagnosed AML cytopathologically confirmed according to the 5th WHO classification

Age between 18 and 75 years

FLT3-ITD mutation as per local IVDR-compliant testing. Positivity is defined as a FLT3-ITD / FLT3-wild type (WT) ratio of ≥ 0.05 (5%))

Eligibility for standard induction chemotherapy

Disqualifiers

Acute promyelocytic leukemia (APL)

BCR-ABL positive leukemia or Ph1-positive chronic myeloid leukemia

History of myeloproliferative neoplasm (MPN), including myelofibrosis, essential thrombocythemia, polycythemia vera

Active central nervous system involvement by AML

Trial design

Design model

Parallel

Treatments tested in this trial

  • Gilteritinib

    Drug

    Cycle 1: 80 mg once daily orally on days 1-28. Cycle 2 - 12: 80mg once daily orally on days 1-28. Cycle 13 - 24: gilteritinib 120 mg once daily orally on days 1-28. Following HSCT, maintenance with gilteritinib (120 mg once daily orally on days 1-28) will be offered for up to 36 cycles and started between day 30 and 90 after hematopoietic stem-cell transplantation (HSCT).

  • Venetoclax

    Drug

    Cycle 1: ramp-up from 100mg on day 1, 200 mg on day 2 and 400 mg on days 3 - 28. Cycle 2 - 12: venetoclax 400 mg once daily orally days 1-7.

  • Azacitidine (AZA)

    Drug

    Cycle 1: 75 mg/m² once daily subcutaneously on days 1-7. Cycle 2 -12: 75 mg/m² once daily subcutaneously on days 1-5. Cycle 13 - 24: 75 mg/m² once daily subcutaneously on days 1-5.

  • Local standard of care (SOC)

    Drug

    Local SOC is "7+3" + Midostaurin (100 mg) or Quizartinib (35.4 mg)

Treatment groups

230 Participants
are divided into 2 treatment groups
Group A: Triplet combination of venetoclax, azacitidine and gilteritinibExperimental treatment 3 interventions
Group B: Local standard of careActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Phase II: Achievement of CR/CRi documented within 6 months from randomization, occurring prior to allografting and before initiation of any post-protocol treatments.

The European LeukemiaNet (ELN) 2022 criteria will be used to evaluate CR/CRi.

Time frame
Within 6 months from randomization
2

Phase III: Overall survival

Time frame
From baseline through study completion, an average of 7 years

Secondary outcomes

1

Achievement of CR/CRi documented within 6 months from randomization, occurring prior to allografting and before initiation of any post-protocol treatments (for the phase III component of the trial only)

Time frame
Within 6 months from randomization
2

Overall survival (for the phase II component of the trial only)

Time frame
From baseline through study completion, an average of 7 years
3

Event-free survival

Event-free survival defined as the time between the date of randomization and the date of relapse, treatment failure or death, whichever occurs first

Time frame
From baseline through study completion, an average of 7 years
4

Incidence of adverse events

Time frame
From baseline through study completion, an average of 7 years

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

European Organisation for Research and Treatment of Cancer - EORTC

Lead sponsor

Fondazione GIMEMA

Collaborator

Astellas Pharma Inc

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: