Ibrutinib, Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

This is an interventional treatment trial for Recurrent Adult Acute Myeloid Leukemia Read More

INCLUSION CRITERIA

• Previous morphologically-confirmed diagnosis of acute myeloid leukemia (AML) based on World Health Organization (WHO) Criteria
• At least one prior chemotherapy regimen to treat AML
• Disease relapse or refractory disease as shown by > 5% blasts in the bone marrow (not attributable to another cause). Administration of hydrea to control high WBC count is permitted.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, or Karnofsky Performance Status (KPS) ≥ 60%
• Life expectancy > 4 weeks
• Platelet count ≥ 10,000/mm3 within 72 hours of initiating the Induction Cycle (platelet transfusion support is allowed)
• Serum creatinine ≤ 2.0 mg/dL within 72 hours of initiating the Induction Cycle
• Total bilirubin ≤ 2.1 mg/dL within within 72 hours of initiating the Induction Cycle (EXCEPTION: If elevation is not due to liver dysfunction, and is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome, or hemolysis of non-hepatic origin)
• Serum glutamic oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST) ] ≤ 3.0 X upper limit of normal (ULN) within 72 hours of initiating the Induction Cycle
• Serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] ≤ 3.0 X ULN within 72 hours of initiating the Induction Cycle
• Baseline prothrombin time (PT)/international normalized ratio (INR) ratio < 3 X ULN within 7 days of initiating the Induction Cycle (for subjects with correctable coagulation abnormalities, coagulation factor support per institutional standard of care for AML is allowed)
• Partial thromboplastin time (PTT) < 3 X ULN within 7 days of initiating the Induction Cycle (for subjects with correctable coagulation abnormalities, coagulation factor support per institutional standard of care for AML is allowed)
• Negative pregnancy test within 14 days prior to study treatment (for Women of reproductive potential only)
• Women of child-bearing potential and men must agree (in ICF) to use adequate contraception (eg, hormonal or barrier methods of birth control; abstinence; sterilized partner) for the duration of study participation
• Ability to understand and the willingness to sign the written informed consent document

EXCLUSION CRITERIA

• Received anticancer therapy (chemotherapy, immunotherapy, radiotherapy, or investigational therapy) within 2 weeks prior to starting study treatment [EXCEPTION: Hydroxyurea (hydrea) to control high white blood cell count is permitted]
• Receiving any other investigational agents within 14 days or 5 effective half lives (whichever is shorter) prior to 1st dose of ibrutinib
• Prior treatment with ibrutinib
• Known unresolved toxicities due to prior anticancer therapy [≥ Grade 2, by Common Terminology Criteria for Adverse Events (CTCAE) v4.03] unless otherwise defined in the inclusion/exclusion criteria (EXCEPTION: alopecia)
• Known acute promyelocytic leukemia (French-American-British Class M3-AML)
• Known active central nervous system (CNS) leukemia
• Prior bone marrow transplant presenting with active uncontrolled graft vs host disease (GvHD)
• Known congenital bleeding disorders, such as hemophilia
• Known history of stroke or intracranial hemorrhage within 6 months prior to study treatment
• Concomitant use of warfarin or other vitamin K antagonists
• Requires treatment with strong CYP3A inhibitors at the time of study enrollment. Washout period is 5 effective half-lives is required prior to 1st dose of ibrutinib
• Requires treatment with strong CYP3A inducers at the time of study enrollment. Washout period is 5 effective half-lives is required prior to 1st dose of ibrutinib
• Known active uncontrolled systemic infection
• Major surgery within 4 weeks of 1st dose of ibrutinib
• Unable to swallow capsules
• Known Malabsorption syndrome
• Known Disease significantly affecting gastrointestinal function
• Resection of the stomach or small bowel
• Uncontrolled symptomatic inflammatory bowel disease
• Ulcerative colitis
• Bowel obstruction, partial or complete
• Congestive heart failure with ejection fraction (EF) < 45%
• Uncontrolled cardiac disease, including uncontrolled cardiac arrhythmia or coronary artery disease (CAD) with active symptoms due to CAD defined as unstable angina
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib; idarubicin; or cytarabine
• Uncontrolled intercurrent illness including, but not limited to:
• Active infection
• Psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant
• Lactating
• Known positive HIV
• Known active hepatitis C
• Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)