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

NCT03686345 | Terminated Phase 2

• 2 other identifiers: REL-AML 001/20172017-002094-18
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Core Binding Factor Acute Myeloid Leukemia (CBF-AML)

Keywords

Midostaurin; Chemotherapy; Relapse Incidence; Overall Survival; Disease Free Survival; Minimal Residual Disease monitoring

Outcome Measures

Primary Outcomes (1)

• Relapse Incidence

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

  2 years

Secondary Outcomes (4)

• Overall survival

  5 years

• Safety assessment - Frequency and severity of adverse events

  Up to 30 days after last dose of study drug

• Disease-free survival

  5 years

• Event-free survival

  5 years

Study Arms (1)

Core binding factor acute myeloid leukemia (CBF-AML)

EXPERIMENTAL

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. 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.

Drug: Midostaurin

Interventions

Midostaurin DRUG

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

Core binding factor acute myeloid leukemia (CBF-AML)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Niguarda Hospital: lead

Study Sites (1)

Ospedale Cà Granda - Niguarda S.C: Ematologia

Milan, 20162, Italy

Location

Related Publications (1)

• 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.

  PMID: 39659145 BACKGROUND

MeSH Terms

Interventions

midostaurin

Study Design

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

Model Details: Core binding factor acute myeloid leukemia (CBF-AML) patients

Study Record Dates

• First Submitted: July 4, 2018
• First Posted: September 26, 2018
• Study Start: July 1, 2018
• Primary Completion: June 30, 2023
• Study Completion: December 31, 2024
• Last Updated: February 25, 2025

Record last verified: 2025-02

Locations

IT (1)