Dasatinib (Sprycel™) in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)

University of Ulm

Status and phase: Completed; Phase 2; Phase 1

Conditions: Acute Myeloid Leukemia (AML)

Treatments: Drug: Cytarabine; Drug: Dasatinib; Drug: daunorubicin

Study type: Interventional

Funder types: Other

Identifiers

NCT00850382

AMLSG 11-08

Details and patient eligibility

About

This is a Phase Ib/IIa open-labeled multi-center trial evaluating the feasibility of dasatinib given after standard induction therapy with daunorubicin (DNR) and cytarabine (ARA-C), after consolidation therapy with high-dose cytarabine (HDAC), and as single agent in a one-year maintenance therapy in patients with newly diagnosed CBF AML.

82 patients with newly diagnosed CBF AML will be enrolled at AMLSG study centers.

All AML patients will be assessed for the CBF fusion genes via the central laboratory of the AMLSG within 48 hours of diagnosis of AML, and only patients with CBF AML will be enrolled into the study.

Enrollment: 89 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Core binding factor (CBF) AML with molecular diagnosis of RUNX1-RUNX1T1 fusion transcript resulting from t(8;21)(q22;q22) (or a variant form) or of CBFB-MYH11 fusion transcript resulting from inv(16)(p13.1q22)/t(16;16)(p13.1;q22) as assessed in one of the central AMLSG reference laboratories.
• Age ≥ 18; there is no upper age limit.
• No prior chemotherapy for leukemia except hydroxyurea for up to 5 days during the diag-nostic screening phase.
• Non-pregnant and non-nursing. Due to the unknown teratogenic potential of dasatinib in humans, pregnant or nursing patients may not be enrolled. Women of childbearing poten-tial (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration. Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control - one highly effective method (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (e.g., latex condom, diaphragm, or cervical cap) - AT THE SAME TIME, at least four weeks before she begins dasatinib therapy. "Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months.
• Men must agree not to father a child and must use a latex condom during any sexual con-tact with women of childbearing potential while taking dasatinib and for 4 weeks after therapy is stopped, even if they have undergone a successful vasectomy.
• Signed written informed consent

Exclusion criteria

• Performance status WHO >2
• Pulmonary edema and/or pleural/pericardial effusion within 14 days of Day 1. If edema/effusion resolves to CTC Grade ≤ 1, patients can be treated with dasatinib.
• Patients with ejection fraction < 50% by echocardiography within 14 days of day 1
• Organ insufficiency (creatinine >1.5x upper normal serum level; bilirubin, AST or AP >2.5x upper normal serum level; heart failure NYHA III/IV; severe obstructive or restrictive ventilation disorder)
• Uncontrolled infection
• Severe neurological or psychiatric disorder interfering with ability of giving an informed consent
• Known positive for HIV
• Bleeding disorder independent of leukemia
• No consent for registration, storage and processing of the individual disease-characteristics and course

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

89 participants in 1 patient group

Dasatinib

Experimental group

Description:

Induction cycle(s): Patients will receive in cycle 1 induction therapy with daunorubicin 60 mg/m2/day administered on days 1 through 3 and cytarabine 200 mg/m2/day administered by continuous IV infusion daily for 7 days (days 1 through 7). Patients will receive dasatinib 100 mg QD on days 8-21. Patients not achieving CR or CRi at the end of cycle 1 will be evaluable to receive a second induction cycle identical in schedule and dosage to the first induction cycle. Consolidation Cycles 1, 2, 3, 4: Patients achieving CR or CRi at the end of cycle 1 will receive consolidation therapy for 4 cy-cles. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (\>60 years: 1 g/m2) q12h, d 1, 3, 5, administered intravenously over three hours. Patients will receive dasatinib 100 mg QD on days 6-28. Maintenance therapy: Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse).

Treatment:

Drug: Dasatinib

Drug: Cytarabine

Drug: daunorubicin