Clinical trial NCT02415608 (phase 2, status: terminated)
Conditions: aggressive systemic mastocytosis, mast cell leukemia, systemic mastocytosis
ICD codes: C96.21, C94.31, C94.32, C94.30, D47.02, C96.21
Drugs: ibrutinib
SMILES: NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1
Reason stopped: 
    slow accrual
  
Eligibility criteria:

        INCLUSION CRITERIA

          -  Diagnosis of systemic mastocytosis per 2008 World Health Organization (WHO) criteria.
             Those with advanced systemic mastocytosis (ASM); mast cell leukemia (MCL); or systemic
             mastocytosis-associated hematological clonal non-mast cell lineage disease (SM-AHNMD)
             required to have at least 1 organ damage finding

          -  Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit
             of normal (ULN); if considered related to ASM/MCL ≤ 5 x ULN

          -  Estimated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault)

          -  Total bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of
             non-hepatic origin); if considered related to ASM/MCL ≤ 3 x ULN

          -  Female subjects must be of non-reproductive potential, or if of childbearing potential
             must have a negative serum pregnancy test upon study entry

          -  Must agree to use highly effective methods of birth control

          -  Written informed consent

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3

          -  Life expectancy > 12 weeks

        EXCLUSION CRITERIA

          -  Received any investigational agent, chemotherapy, interferon-alpha, or
             2-chlorodeoxyadenosine (2-CdA, cladribine) within 30 days prior to day 1; or
             monoclonal antibody ≤ 6 weeks prior to first administration of study treatment
             (patients with an AHNMD with progressive leukocytosis who require control of their
             counts are permitted to receive hydroxyurea)

          -  Diagnosis of AHNMD requiring immediate cytoreductive therapy or targeted drugs (eg,
             acute myeloid leukemia [AML])

          -  History of other malignancies, except:

               -  Malignancy treated with curative intent and with no known active disease present
                  for ≥ 3 years before the first dose of study drug, and at low risk for recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease

          -  Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc.,
             or chronic administration [> 14 days] of > 10 mg/day of prednisone) within 28 days of
             the first dose of study drug

          -  Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

          -  Systemic treatment for infection completed ≤ 14 days before the first dose of study
             drug

          -  Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved
             to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade 0 or 1, or
             to the levels dictated in the inclusion/exclusion criteria with the exception of
             alopecia

          -  Known bleeding disorders (eg, severe von Willebrand's disease) or severe hemophilia

          -  History of stroke or intracranial hemorrhage within 6 months prior to enrollment

          -  Known history of human immunodeficiency virus (HIV) or

          -  Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)

          -  Major surgery within 4 weeks of first dose of study drug

          -  Any life-threatening illness, medical condition, or organ system dysfunction that
             could compromise the subject's safety or put the study outcomes at undue risk

          -  Currently active, clinically significant cardiovascular disease, such as uncontrolled
             arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart
             Association Functional Classification; or a history of myocardial infarction, unstable
             angina, or acute coronary syndrome within 6 months prior to randomization

          -  Unable to swallow capsules or malabsorption syndrome

          -  Disease significantly affecting gastrointestinal function

          -  Resection of the stomach or small bowel

          -  Symptomatic inflammatory bowel disease

          -  Ulcerative colitis

          -  Partial or complete bowel obstruction

          -  Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor

          -  Lactating or pregnant

          -  Unwilling or unable to participate in all required study evaluations and procedures

          -  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)

          -  Known hypersensitivity to any excipient contained in the drug

          -  Received hematopoietic growth factor support within 14 days of day 1 of ibrutinib
             (Jehovah's witnesses may be given an erythropoiesis-stimulating agent before and
             during the trial in lieu of red blood cell transfusions but anemia and/or red blood
             cell (RBC) transfusion dependence cannot be used for response assessment in these
             patients)

          -  Presence of the factor interacting with poly(A) polymerase alpha (PAPOLA) and cleavage
             and polyadenylation specific factor 1 (CPSF1) (FIP1L1)-platelet-derived growth factor
             receptor, alpha polypeptide (PDGFRalpha) fusion even with resistance to imatinib (such
             patients are no longer defined as systemic mastocytosis by the WHO)

          -  Received any treatment with ibrutinib prior to study entry

          -  The concomitant use of warfarin or other vitamin K antagonists unless felt to be of
             significant clinical need; low molecular weight heparin or other anticoagulants may be
             used instead if anticoagulation is required