Avapritinib With Decitabine in Patients With SM-AHN

Exclusion Criteria

• •History of decitabine use with documented disease progression of AHN by 2006 IWG MDS response criteria while on decitabine.
• •History of avapritinib use with documented progression of mastocytosis while on avapritinib per m-IWG-MRT-ECNM criteria.
• •History of treatment with decitabine in combination with avapritinib.
• •Use of azacitidine within 4 weeks of first dose of study drug.
• •Diagnosis of AML defined as presence of ≥ 20% myeloblasts in the peripheral blood or bone marrow or presence of a myeloid sarcoma.
• •Patients who are receiving any other investigational agents or are participating in another interventional study.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacytidine, decitabine, cedazuridine, avapritinib, propylene glycol, mannitol (only for patients receiving azacytidine).
• •History of intracranial hemorrhage or need for full anticoagulation with warfarin, direct oral anticoagulant, or treatment dose low molecular weight heparin (LMWH), or any condition that, in the investigator's opinion, would put the patient at an increased risk for spontaneous, unprovoked hemorrhage such as: I) Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within one year of the first dose of study drug II) Presence of a vascular aneurysm in the brain III) Known intracranial arteriovenous malformation (AVM).
• •Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.
• •Patient has a QT interval corrected using Fridericia's formula (QTcF) \> 480 msec.
• •Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease (GVHD), or requiring transplant related immunosuppression.
• •Patients receiving any medications or substances that are strong or moderate CYP3A inhibitors or strong or moderate CYP3A inducers. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• •Participants with uncontrolled intercurrent illness.
• •Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• •Pregnant women are excluded from this study because, based on the mechanism of action and data from animal reproduction studies, in utero exposure to avapritinib may cause fetal harm.
• •Women who are breast feeding.
• •Patient is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
• •Patient has a primary brain malignancy or metastases to the brain.
• •Patient has had a major surgical procedure within 14 days of the first dose of study drug. Surgical procedures such as central venous catheter placement, bone marrow (BM) biopsy, and feeding tube placement are considered minor surgical procedures.
• •Patient has eosinophilia and known positivity for the FIP1L1-PGDFRA fusion, unless the patient has demonstrated relapse or progressive disease (PD) on prior imatinib therapy. Patients with eosinophilia (\> 1.5 × 109/L), who do not have a detectable KIT D816 mutation, must be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR).
• •Patient is participating in another interventional clinical study.