OX40, Venetoclax, Avelumab, Glasdegib, Gemtuzumab Ozogamicin, and Azacitidine in Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• ARMS A-G: RR AML: Patients with AML who are refractory or relapsed (any salvage) with no available therapies or not candidates for available therapies. For patients with prior MDS or chronic myelomonocytic leukemia (CMML) or myeloproliferative neoplasm (MPN) who transformed to AML, therapy received for MDS, CMML, or MPN is NOT considered as prior therapy for AML with the exception of MDS or CMML treated with hypomethylating agents (HMAs). Patients with MDS or CMML treated with HMA therapies who progress to AML, and have no available therapies or are not candidates for available therapies, will be eligible at the time of progression to AML.
• Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is permitted.
• Eastern Cooperative Oncology Group (ECOG) performance status = = 40 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
• Patients must provide written informed consent.
• In the absence of rapidly progressive disease, the interval from prior treatment to the time of initiation of protocol therapy will be at least 14 days for prior anti-leukemic therapy, with the exception of hydroxyurea as noted below, OR at least 5 half-lives for cytotoxic/noncytotoxic agents, whichever is shorter. The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document. The toxicity from prior therapy should have resolved to grade = = 3 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
• Patients with a known history of severe interstitial lung disease or severe pneumonitis or active pneumonitis/pneumonia or pulmonary pathology that is not well controlled in the opinion of the treating physician and/or principal investigator (PI).
• Clinically significant (i.e., active) cardiovascular disease: acute cerebral vascular accident/stroke ( = New York Heart Association classification class II), or serious cardiac arrhythmia requiring medication.
• Ejection fraction 1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy grade = = 2 (eg, atrial fibrillation) or corrected QT interval by Fridericia's correction formula (QTcF) interval > 470 msec within 4 weeks prior to starting the study drug