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INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib PO QD on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity \>= 20% and leukemia blasts \>= 5%) receive a second course of induction therapy.

INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO QD on days 6-19. Patients achieving complete response receive consolidation therapy.

CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.

Daunorubicin Hydrochloride

Laboratory Biomarker Analysis

Guido Marcucci

This phase II trial studies the side effects and how well giving combination chemotherapy together with dasatinib works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with dasatinib may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of dasatinib 100 mg/day given after intensive induction (daunorubicin hydrochloride \[daunorubicin\]/cytarabine), and consolidation chemotherapy (high-dose cytarabine) and as single agent in maintenance therapy to newly diagnosed patients with core binding factor acute myeloid leukemia (AML).

II. 30-day survival rate during induction (the lack of early/hypoplastic death).

III. The absence of pleural or pericardial effusion, and absence of liver toxicity that exceeds grade 2.

SECONDARY OBJECTIVES:

I. To assess clinical outcomes such as event-free survival (EFS), complete response (CR) rate, cumulative incidence of relapse (CIR), cumulative incidence of death (CID), disease-free survival (DFS), and overall survival (OS).

II. To describe the frequency and severity of adverse events of patients treated on this study during induction, consolidation, and continuation therapy.

III. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.

OUTLINE:

INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO) once daily (QD) on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity \>= 20 % and leukemia blasts \>= 5%) receive a second course of induction therapy.

INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO once a day on days 6-19. Patients achieving complete response receive consolidation therapy.

CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO QD on days 6-26 or 7-27. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.

CONTINUATION THERAPY: Patients receive dasatinib PO on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then every year for up to 10 years from study entry.

Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

A Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517) and Continuation Therapy With Dasatinib Alone in Newly Diagnosed Patients With Core Binding Factor Acute Myeloid Leukemia (AML)

Percentage of participants who were alive 30 days after starting induction treatment.

Event free survival (EFS) is defined as the time from registration to failure to achieve complete remission (CR), relapse after CR is attained or death, whichever comes first. The 1 year EFS rate with 95% CI was estimated using the Kaplan-Meier method,

Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts).

Percentage of participants who achieve a CR. Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x 10\^9/L and platelet count \> 100 x 10\^9/L, and normal bone marrow differential (\< 5% blasts).

Disease free survival (DFS) is defined as the time from achievement of CR to relapse or death, whichever comes first. The 3 year DFS rate with 95% CI was estimated using the Kaplan-Meier method.

Overall survival (OS) is defined as time from registration to death. The 3 year OS rate with 95% CI was estimated using the Kaplan-Meier method.

National Cancer Institute (NCI)

CONTINUATION THERAPY: dasatinib PO (100 mg) once daily for 12 months or relapse.

Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib)

INDUCTION THERAPY: daunorubicin hydrochloride IV (60 mg/m\^2)on days 1-3, cytarabine IV (200 mg/m\^2) continuously over 168 hours on days 1-7, and dasatinib PO (100 mg) once daily on days 8-21. Patients achieving a response go to consolidation therapy, and patients not achieving a receive a second course of induction therapy.

CONSOLIDATION THERAPY: high-dose cytarabine IV (patients \< Age 60: 3000 mg/m\^2, Age \>= 1000 mg/m\^2)over 3 hours on days 1, 3, and 5, and dasatinib PO (100 mg) once daily on days 6-26. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.

CONTINUATION THERAPY: dasatinib PO (100 mg) once daily for 12 months or relapse.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Guido Marcucci, M.D.

30 Day Survival Rate

Event-free Survival

Complete Response Rate

Cumulative Incidence of Relapse

Cumulative Incidence of Death

Disease-free Survival

Overall Survival

Overall Study

The treatment group will receive avapritinib orally. The dosage is 100mg to 300mg qd, allowed to combine with other chemotheray drugs.

Avapritinib

Suning Chen

Haiping Dai

Suning Chen, PhD

AML with t(8; 21)(q22; q22) or inv(16)(p13; q22)/t(16; 16)(p13; q22) is known as CBF-AML. KIT mutations are common in CBF-AML, which have a worse prognosis.This study is aimed to evaluate the efficacy of Avapritinib, an highly specific inhibitor of the KIT gene, in CBF-AML with KIT mutations.

Acute Myeloid Leukemia (AML) with the chromosomal abnormality of t(8; 21)(q22; q22) or inv(16)(p13; q22)/t(16; 16)(p13; q22) is known as the Core Binding Factor AML (CBF-AML). KIT mutation is a common mutation in CBF-AML, which is more likely to relapse and have a worse prognosis.

Avapritinib is an oral tyrosine kinase inhibitor (TKI) with selective inhibitory activity against KIT and PDGFRA. Avapritinib has been approved by FDA for the treatment of gastrointestinal stromal tumors(GIST) with PDGFRA mutations and Advanced systemic mastocytosis (AdvSM). However, the efficacy of avapritinib in AML with KIT mutations is uncertain.

This prospective, multicenter clinical study of the efficacy and safety of avapritinib in relapsed refractory or molecular minimal residual disease (MRD)-positive AML with KIT mutations.

Avapritinib in CBF-AML With KIT Mutations

Avapritinib in Relapsed Refractory or MRD-positive CBF-AML With KIT Mutations

The proportion of participants who achieve Composite complete remission (CRc)，which includes complete remission (CR)、CR with partial hematologic recovery (CRh)、CR with incomplete blood count recovery (CRi) and morphology leukemia free (MLFS) based on response criteria for AML.

The proportion of participants who achieve a negative molecular MRD.

The Kaplan-Meier method will be used to assess PFS probabilities.

The Kaplan-Meier method will be used to assess OS probabilities.

Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients with AEs will be estimated, along with the 95% credible interval.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia	NCT01238211	Acute Myeloid L... Acute Myeloid L... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... Core Binding Fa... Secondary Acute... Therapy-Related...	Cytarabine Dasatinib Daunorubicin Hy... Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Avapritinib in CBF-AML With KIT Mutations	NCT05821738	Core Binding Fa... KIT Mutation-Re...	Avapritinib	15 Years -	The First Affiliated Hospital of Soochow University
Avapritinib in CBF-AML With KIT Mutations	NCT05821738	Core Binding Fa... KIT Mutation-Re...	Avapritinib	15 Years -	The First Affiliated Hospital of Soochow University

Spots Global Cancer Trial Database for core binding factor acute myeloid leukemia