Dasatinib in Combination with Chemotherapy in Treating Younger Patients with Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia

Inclusion Criteria

• Patients must have histologically confirmed relapsed or refractory AML and meet the following criteria: * Relapsed disease is defined as AML is in 1st or greater marrow relapse * Refractory disease is defined as AML which failed to go into remission after 1st or greater relapse, OR AML which failed to go into remission after two or more induction attempts from original diagnosis
• Patients must have >= 5% blasts by morphology in the bone marrow OR molecular evidence of at least 0.1% leukemic blasts in the bone marrow
• All patients must have definitive evidence of t(8;21) or inv(16) by a Clinical Laboratory Improvement Amendments (CLIA) approved cytogenetics laboratory from initial diagnosis
• Patients may have CNS or other sites of extramedullary disease; no cranial irradiation is allowed during the protocol therapy
• Lansky >= 50 for patients =< 16 years old; Karnofsky >= 50 for patients > 16 years old
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiation therapy prior to entering this study
• 14 days must have elapsed since the completion of myelosuppressive therapy; individuals may have received any of the following medications within 14 days without a “wash-out” period: * Hydroxyurea * Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine
• Patients who have experienced their relapse after a hematopoietic stem cell transplant (HSCT) are eligible, provided all of the following are met: * No evidence of acute or chronic graft-versus-host disease (GVHD) * At least 14 days off all medications for GVHD * At least 60 days post-transplant at the time of enrollment
• It must have been at least 7 days since the completion of therapy with granulocyte colony stimulating factor (GCSF) or other growth factors at the time of enrollment; it must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta)
• At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the principal investigator
• At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody. (i.e. gemtuzumab = 36 days)
• At least 42 days must have elapsed after the completion of any type of immunotherapy, e.g. tumor vaccines
• Craniospinal radiation therapy (XRT) is prohibited during protocol therapy; no washout period is necessary for radiation given to non-CNS chloromas; >= 90 days must have elapsed if prior traumatic brain injury (TBI) or craniospinal XRT
• Patients must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) 70ml/min/1.73 m^2 OR a normal serum creatinine based on age/gender in the chart below: * Age: 1 month to < 6 months; maximum serum creatinine: male 0.4 mg/dL; female 0.4 mg/dL * Age: 6 months to < 1 year; maximum serum creatinine: male 0.5 mg/dL; female 0.5 mg/dL * Age: 1 to < 2 years; maximum serum creatinine: male 0.6 mg/dL; female 0.6 mg/dL * Age: 2 to < 6 years; maximum serum creatinine: male 0.8 mg/dL; female 0.8 mg/dL * Age: 6 to < 10 years; maximum serum creatinine: male 1 mg/dL; female 1 mg/dL * Age: 10 to < 13 years; maximum serum creatinine: male 1.2 mg/dL; female 1.2 mg/dL * Age: 13 to < 16 years; maximum serum creatinine: male 1.5 mg/dL; female 1.4 mg/dL * Age: >= 16 years; maximum serum creatinine: male 1.7 mg/dL; female 1.4 mg/dL
• Patients must have a direct bilirubin < 1.5 x upper limit of normal (ULN) for age or normal; these criteria may be waived for patients with known or suspected liver involvement by leukemia following review and approval by the study chair or vice chair
• Patients must have an alanine transaminase (ALT) < 5 x ULN for age; these criteria may be waived for patients with known or suspected liver involvement by leukemia following review and approval by the study chair or vice chair
• Patients must have a shortening fraction greater than or equal to 27% by echocardiogram, OR ejection fraction greater than or equal to 50% by radionuclide angiogram (multigated acquisition [MUGA])
• Patients must not have any evidence of dyspnea at rest, exercise intolerance, and must have a pulse oximetry > 94% at sea level
• Patients with a seizure disorder may be enrolled if well controlled on anticonvulsants at a dose that has been stable for at least 14 days; however, drugs that induce cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, and phenobarbital) should be avoided
• Patients must meet the following conditions related to reproductive health: * Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment * Female patients with infants must agree not to breastfeed their infants while on this study * Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment

Exclusion Criteria

• Patients will be excluded if they have a known allergy to any of the drugs used in the study
• Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection of which they exhibit ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment; the patient needs to be off all pressor medications and have negative blood cultures for at least 48 hours
• Patients with any clinically significant cardiovascular disease including the following: * Myocardial infarction or ventricular tachyarrhythmia within 6 months * Prolonged QTc > 480 msec by the Fridericia correction * Major conduction abnormality, such as 2nd or 3rd degree heart block or symptomatic bundle branch block, unless a cardiac pacemaker is present
• Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation; the patient may be referred to a cardiologist at the discretion of the treating physician; patients with underlying cardiopulmonary dysfunction should be excluded from the study
• Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period
• Patients refractory to red blood cell or platelet transfusions
• Patients receiving anti-coagulation therapy are excluded
• Patients will be excluded if there is a need to administer drugs that inhibit platelet function, such as aspirin or clopidogrel; for such medications a wash-out period of >= 7 days is required prior to starting dasatinib
• Patients must not be receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John’s wort
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results
• Patients with Down syndrome and deoxyribonucleic acid (DNA) fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded