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Core Binding Factor Acute Myeloid Leukemia (CBF-AML)Phase 2AML FLT3NCT03686345

Midostaurin Associated With Standard Chemotherapy in Patients With Core-binding Factor Leukemia

A Phase 2 study testing Midostaurin in people with Core Binding Factor Acute Myeloid Leukemia (CBF-AML), run by Niguarda Hospital at 1 site in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this single-arm, open label, phase-II trial, is to determine whether the association of Midostaurin to standard induction, consolidation therapy and in maintenance therapy as single agent, is effective in decrease relapse incidence, in patients with CBF-AML. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Midostaurin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteItaly
Study dates
1 Jul 2018to 31 Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent must be obtained prior to any screening procedures.
  • Patients must be 18 to 65 years of age at the time of signing informed consent.
  • Patients must have an unequivocal diagnosis of de novo-CBFL, prior to start midostaurin, documented by rearrangement of Core Binding Factor (CBF) genes, namely AML1-ETO and CBFB-MYH11, either with observation of t(8;21)(q22;q22) or inv(16)(p13; q32)/t(16;16)(p13; q32) by conventional cytogenetics or hybridization techniques or detection of fusion genes by PCR-polymerase chain reaction
  • Patients must be fit to receive an anthracycline/AraC-based induction therapy (i.e. Ara-C 100 mg/m2 or 200 mg/m2 i.v. day, by continuous infusion for 7 days and Idarubicin 12 mg/m2 i.v. day or daunomycin 60 mg/m2 on days 1, 3 and 5)
  • Patients must have an ECOG-Eastern Cooperative Oncology Group Performance Status of ≤ 2.
  • Patients must have Total Bilirubin ≤ 1.5 x ULN, and AST or ALT ≤ 2.5 x ULN.
  • Patients must have Serum Creatinine ≤ 1.5 x ULN.
  • Women of child-bearing potential must have a negative pregnancy test before starting the protocol.

Who cannot join

  • Prior therapy for AML with the following exceptions:
  • emergency leukapheresis
  • emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 7 days
  • Central nervous system involvement
  • Presence of any uncontrolled bacterial, viral or fungal infection
  • Known human immunodeficiency virus (HIV) positive
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  • An active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. Patients whose disease is controlled under antiviral therapy should not be excluded.
  • Presence of other active malignancies
  • QTc > 470 msec (Bazett formula) on screening ECG
  • Presence of significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
  • Myocardial infarction, unstable angina and/or congestive heart failure within 3 months prior to randomization
  • History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia
  • Uncontrolled hypertension
  • Taking medications that are known to be associated with Torsades de Pointes.
  • History of hypersensitivity to any drugs or metabolites of similar chemical classes as the study treatment.
  • Pregnancy statements and contraception requirements:
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 4 months after stopping medication. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject
  • Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should also add a barrier method of contraception, particularly as it is currently unknown whether midostaurin may reduce the effectiveness of hormonal contraceptives. Sexually-active males unless they use a condom during intercourse with females of reproductive potential or pregnant women and for at least 4 months after stopping treatment to avoid conception or embryo-fetal harm.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Ospedale Cà Granda - Niguarda S.C: Ematologia

    Milan, 20162

Other trials in Italy

About this study

Official title: Prospective Evaluation of a Continuation Therapy With Midostaurin in Adult Patients With Core-binding Factor Leukemia and Integrated Genetic Analysis: a Multi-center Phase II Study

The purpose of this single-arm, open label, phase-II trial, is to determine whether the association of Midostaurin to standard induction, consolidation therapy and in maintenance therapy as single agent, is effective in decrease relapse incidence, in patients with CBF-AML. The single-arm, open label, phase-II study is based on data obtained from previous clinical and pre-clinical studies, obtained by use of Midostaurin in patients with Acute Myeloid Leukemia (with or without FLT3 mutations) and in patients with Mast cell disorders (characterized by mutations in the C-KIT gene). The investigators believe that Midostaurin, associated with standard therapy Anthracycline/AraC Induction, to the consolidation regimen with high doses of araC and maintenance therapy to single agent in patients with acute myeloid leukemia core-binding factor can significantly reduce the incidence of recurrence of the disease, occurring in 40-50% of cases treated with standard therapy

Read the detailed description

In this prospective, Interventional, Single-Arm, Open-Label, Phase-II Trial aims at demonstrating a decrease in the 2-year Relapse Incidence (RI) and in the 2-year Cumulative Relapse Incidence among the Midostaurin-treated patients compared to a cohort of historical controls. The investigators established that a 20% net reduction in the 2-year RI may be a clinically significant goal. So the investigators set our RI objective at 28%. Furthermore, the investigators will assess if the experimental treatment may obtain an increased 5-years Overall, Disease-Free and Event free Survival. The safety profile of Midostaurin given in combination with induction and consolidation chemotherapy and as a single agent in maintenance in CBFL patients will also be assessed.

Being tested
Midostaurin
Keywords
Midostaurin, Chemotherapy, Relapse Incidence, Overall Survival, Disease Free Survival, Minimal Residual Disease monitoring

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MidostaurinDrug

    Midostaurin associated with standard chemotherapy in patients with core-binding factor leukemia

Study groups in NCT03686345
Study groupRoleWhat they receive
Core binding factor acute myeloid leukemia (CBF-AML)ExperimentalPatients must have an unequivocal diagnosis of de novo-CBFL, prior to start midostaurin, documented by rearrangement of Core Binding Factor (CBF) genes, namely AML1-ETO and CBFB-MYH11. The experimental arm involves the administration of Midostaurin orally 50 mg (two 25 mg tablets) twice a day, from the end of induction chemotherapy, for 14 days. Patients should take Midostaurin at approximately 12 hours intervals. During all consolidation cycles, Midostaurin 50 mg (two 25 mg tablets) is administered orally twice a day, on days 8-21. Patients in complete remission after 3 cycles of remission consolidation therapy, will receive Midostaurin continuation therapy for 12 months. Midostaurin 50 mg (two 25 mg tablets) will be given orally twice a day for 12 months.
Receives: Drug: Midostaurin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Relapse Incidence

    To show that the percentage of relapsed patients is 28% or below

    Measured: 2 years

Secondary outcomes (4)

  1. Overall survival

    To determine overall survival from achievement of first complete remission

    Measured: 5 years

  2. Safety assessment - Frequency and severity of adverse events

    Incidence of toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Frequency and severity of adverse events will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.

    Measured: Up to 30 days after last dose of study drug

  3. Disease-free survival

    To determine disease-free survival from achievement of first complete remission

    Measured: 5 years

  4. Event-free survival

    To determine event-free survival from diagnosis

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2018
  2. Study start1 Jul 2018
  3. Primary completion30 Jun 2023
  4. Study completion31 Dec 2024

Why it stopped: didn't reach the primary endpoint

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Core binding factor acute myeloid leukemia (CBF-AML) patients
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03686345
Sponsor's protocol ID
REL-AML 001/2017
Other IDs
2017-002094-18, 2017
Acronym
AML FLT3
Status last verified
Feb 2025
First submitted
4 Jul 2018
Last updated
25 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Cairoli R, Gatti A, Grillo G, Stefanucci MR, Di Camillo B, Fumagalli M, Krampera M, Nadali G, Zappasodi P, Borlenghi E, Todisco E, Ubezio M, Bernardi M, Molteni A, Basilico C, Turrini M, Greco R, Mancini V, Riva M, Bernasconi DP, Brando B, Veronese SM, Beghini A. Efficacy of Midostaurin Combined With Intensive Chemotherapy in Core Binding Factor Leukemia: A Phase II Clinical Trial. Am J Hematol. 2025 Feb;100(2):346-349. doi: 10.1002/ajh.27547. Epub 2024 Dec 10.

    PubMed 39659145

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Midostaurin in people with Core Binding Factor Acute Myeloid Leukemia (CBF-AML), run by Niguarda Hospital at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: didn't reach the primary endpoint). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapse Incidence (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03686345, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2025.

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