Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia

• Status: Withdrawn
• Trial end date: 2017-12-15
• Target enrollment: 0
• Participant gender: All

Summary

This study will examine the appropriate dose and side effects of dasatinib, when it is given with the standard of care chemotherapy for children and adolescents with Acute Myeloid Leukemia (AML).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Treatments: Cytarabine; Dasatinib; Fludarabine; Fludarabine phosphate; Idarubicin; Vidarabine

Criteria

Inclusion Criteria:

• Histologically confirmed relapsed or refractory Acute Myeloid Leukemia (AML) and meet the following criteria: Relapsed disease is defined as AML 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

• ≥ 5% blasts by morphology in the bone marrow or molecular evidence of at least 0.1% leukemic blasts in the bone marrow

• Definitive evidence of t(8;21) or inv(16) by a CLIA approved cytogenetics laboratory from initial diagnosis

• 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

• Have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiation therapy prior to entering this study

• Have adequate renal and hepatic functions

• A shortening fraction greater than or equal to 27% by echocardiogram, OR ejection fraction greater than or equal to 50% by radionuclide angiogram (MUGA)

• 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

• Female participants of childbearing potential must have a negative urine or serum pregnancy test confirmed within 24 hours prior to enrollment

• Female participants with infants must agree not to breastfeed their infants while on this study

• Male and female participants 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:

• Known allergy to any of the drugs used in the study

• 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

• Any clinically significant cardiovascular disease including: 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

• Plans to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period

• Refractory to red blood cell or platelet transfusions

• Receiving anti-coagulation therapy

• A need to administer drugs that inhibit platelet function, such as aspirin or clopidogrel

• Receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's Wort

• 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

• Individuals with Down syndrome and DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome)