Panobinostat, Fludarabine Phosphate, and Cytarabine in Treating Younger Patients with Refractory or Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome

Inclusion Criteria

• Participants must have a diagnosis of AML or MDS and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT) * Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy * Patients with AML must have>= 5% leukemic blasts in the bone marrow or increasing levels of minimal residual disease (MRD) in the bone marrow as assessed by flow cytometry; if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood
• Direct bilirubin =< 1.5 x institutional upper limit of normal (IULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase ALT (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
• Creatinine =< 1.5 x ULN for age
• Serum albumin > 3.0 g/dl
• Left ventricular ejection fraction >= 40% or shortening fraction >= 25%
• Patients must be able to swallow capsules
• Performance status: Lansky >= 50 for patients who are =< 16 years old and Karnofsky >= 50% for patients who are > 16 years old
• Patients must have fully recovered from the acute effects of all prior therapy and must meet the following criteria: * At least 14 days must have elapsed since the completion of myelosuppressive therapy * At least 24 hours must have elapsed since the completion of low-dose chemotherapy, such as hydroxyurea or low-dose cytarabine (up to 200 mg/m^2/day) * For patients who have received prior HSCT, there can be no evidence of graft-versus-host disease (GVHD) and greater than 60 days must have elapsed since the HSCT; patients cannot be receiving therapy, including steroids, for the treatment or prevention of GVHD; all such medications must be discontinued at least 24 hours prior to enrollment
• Body surface area: the minimum body surface area (BSA) allowed for enrollment at dose level 1 to 0.85 m^2; the minimum for dose level 2 is BSA = 0.6 m^2 and the minimum for dose level 3 is BSA = 0.42 m^2

Exclusion Criteria

• Must not be pregnant or breastfeeding; female patients who are sexually active and of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients who are sexually active must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; for both male and female patients who are sexually active, effective methods of contraception must be used throughout the study and for three months following the last dose; abstinence is an acceptable form of contraception
• Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes are not eligible
• Use of investigational agents within 30 days
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, study participation, follow up, or interpretation of study research
• Uncontrolled infection within one week of the first dose; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable
• Known human immunodeficiency virus infection (pre-study testing not required)
• Patient with diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 2; (CTCAE version 4.0)
• Impaired cardiac function or clinically significant cardiac diseases, history of arrhythmia (including ventricular fibrillation or torsade de pointes), bradycardia < 50 beats per minute (bpm), screening electrocardiogram (ECG) with prolonged corrected QT (QTc) (> 450 msec), uncontrolled hypertension or any history or presence of sustained ventricular tachyarrhythmia
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
• Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting treatment; granisetron may be administered, but antiemetics associated with QT prolongation (e.g., ondansetron) are not allowed