Combination of Sorafenib With Standard Therapy in Newly Diagnosed Adult CBF AML

NCT05404516 | Unknown Phase 2 DMC

• 1 other identifier: Sorafenib-CBF AML-2022
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

Core-binding factor acute myeloid leukemia accounts for 10-15% of AML and is categorized as favorable-risk AML. However, the 5-year CIR was up to 40% in this group of patients. Emerging data show that a high frequency of mutations and/or high expression of KIT in CBF AML. Sorafenib is a multitargeted TKI, thus the purpose of this study is to evaluate the safety and efficacy of sorafenib combined with standard therapy in CBF AML.

Conditions

Core Binding Factor Acute Myeloid Leukemia

Keywords

Core Binding Factor Acute Myeloid Leukemia; Sorafenib; CMR (Complete Molecular Remission)

Outcome Measures

Primary Outcomes (1)

• CMR (Complete Molecular Remission)

  CMR in BM after 4 cycles of chemotherapies

  1 year

Secondary Outcomes (4)

• Overall survival

  3 year

• Leukemia-free survival

  3 year

• Cumulative incidence of relapse

  3 year

• Adverse effects

  1 year

Study Arms (2)

Sorafenib

EXPERIMENTAL

Induction cycle(s): IA3+7. Patients will receive sorafenib 400 mg BID on days 8-21. Consolidation Cycle 1: IA3+3. Patients will receive sorafenib 400 mg BID on days 1-21. Consolidation Cycles 2-4: MDAC. Patients will receive sorafenib 400 mg BID on days 1-21. Maintenance therapy: Single agent sorafenib 400 mg BID for one year.

Drug: Sorafenib; Drug: Idarubicin; Drug: Cytarabine

Standard therapy

ACTIVE COMPARATOR

Induction cycle(s): IA3+7. Consolidation Cycle 1: IA3+3. Consolidation Cycles 2-4: MDAC.

Drug: Idarubicin; Drug: Cytarabine

Interventions

Sorafenib DRUG

Induction cycle(s): 400 mg BID on days 8-21. Consolidation cycles 1-4: 400 mg BID on days 1-21. Maintenance therapy: 400 mg BID for one year.

Sorafenib

Idarubicin DRUG

Induction cycle(s): 12 mg/m2/day on days 1-3. Consolidation cycle 1: 8 mg/m2/day administered on days 1-3.

Sorafenib; Standard therapy

Cytarabine DRUG

Induction cycle(s): 100 mg/m2 by continuous IV infusion for 24 hours on days 1-7. Consolidation cycles 1-4: 2 g/m2/12h on days 1-3.

Sorafenib; Standard therapy

Eligibility Criteria

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

You may qualify if:

• Patients must have an unequivocal diagnosis of de novo-CBF AML, prior to start therapy, documented by rearrangement of Core Binding Factor (CBF) genes, namely RUNX1/RUNX1T1 and CBFB/MYH11.
• Age 18 to 65 years old with ECOG performance status 0-2.
• Sign informed consent form, have the ability to comply with study and follow-up procedures.
• 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

• Nanfang Hospital, Southern Medical University: lead
• Guangzhou First People's Hospital: collaborator
• Guangzhou Panyu Central Hospital: collaborator
• Institute of Hematology & Blood Diseases Hospital, China: collaborator
• Peking University People's Hospital: collaborator
• Shenzhen Hospital of Southern Medical University: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator

Study Sites (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

Related Publications (3)

• Rucker FG, Agrawal M, Corbacioglu A, Weber D, Kapp-Schwoerer S, Gaidzik VI, Jahn N, Schroeder T, Wattad M, Lubbert M, Koller E, Kindler T, Gotze K, Ringhoffer M, Westermann J, Fiedler W, Horst HA, Greil R, Schroers R, Mayer K, Heinicke T, Krauter J, Schlenk RF, Thol F, Heuser M, Ganser A, Bullinger L, Paschka P, Dohner H, Dohner K. Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group. Blood. 2019 Nov 7;134(19):1608-1618. doi: 10.1182/blood.2019001425.

  PMID: 31554635 BACKGROUND

• Paschka P, Schlenk RF, Weber D, Benner A, Bullinger L, Heuser M, Gaidzik VI, Thol F, Agrawal M, Teleanu V, Lubbert M, Fiedler W, Radsak M, Krauter J, Horst HA, Greil R, Mayer K, Kundgen A, Martens U, Heil G, Salih HR, Hertenstein B, Schwanen C, Wulf G, Lange E, Pfreundschuh M, Ringhoffer M, Girschikofsky M, Heinicke T, Kraemer D, Gohring G, Ganser A, Dohner K, Dohner H. Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial. Leukemia. 2018 Jul;32(7):1621-1630. doi: 10.1038/s41375-018-0129-6. Epub 2018 Apr 17.

  PMID: 29720733 BACKGROUND

• Rollig C, Serve H, Huttmann A, Noppeney R, Muller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Kramer A, Schafer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hanel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanss C, Repp R, Heits F, Durk H, Hase J, Klut IM, Illmer T, Bornhauser M, Schaich M, Parmentier S, Gorner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. doi: 10.1016/S1470-2045(15)00362-9. Epub 2015 Nov 6.

  PMID: 26549589 BACKGROUND

MeSH Terms

Interventions

Sorafenib; Idarubicin; Cytarabine

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Qifa Liu

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pengcheng Shi

CONTACT

+86-020-62787883; shpch283@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 31, 2022
• First Posted: June 3, 2022
• Study Start: January 1, 2020
• Primary Completion: August 31, 2022
• Study Completion: December 31, 2023
• Last Updated: June 3, 2022

Record last verified: 2022-05

Locations

CN (1)