Clinical trial NCT02343679 (phase 2, status: withdrawn)
Conditions: hematologic malignancies
ICD codes: E70.338, E70.339, P09.3, O28.0, P61.8, P61.9, T45.8X1A
Drugs: ceritinib
SMILES: CC(C)OC1=C(NC2=NC=C(Cl)C(N2)=NC2=CC=CC=C2S(=O)(=O)C(C)C)C=C(C)C(=C1)C1CCNCC1
Reason stopped: 
    no accrual due to rarity of disease.
  
Eligibility criteria:

        Inclusion Criteria:

          -  Alk+R/R hematologic malignancy including but not limited to ALK+ALCL or ALK+LBCL > 1
             prior standard cytotoxic regimen

          -  Age >18

          -  ECOG performance status <2

          -  Evidence of measurable or evaluable disease

          -  Toxicities ≤ grade 2 due to prior therapies Exception: any grade alopecia

          -  Platelets >75 x 109/L

          -  ANC>1.5 x 109/L

          -  AST/ALT<3.0 x ULN, except liver involvement by their lymphoma, include if AST/ALT<5 x
             ULN.

          -  Total Bilirubin<1.5 x ULN, (includes gilbert's syndrome if total bilirubin <3.0 x ULN
             and direct bilirubin <1.5 x ULN)

          -  Potassium, magnesium, total calcium and phosphorous > lower limits of normal

          -  Calculated or measured CrCl> 30ml/min

          -  Ability to provide written informed consent

          -  Willing/able to comply with scheduled visits, treatment plans, laboratory tests and
             other procedures

          -  Women/men of reproductive potential must agree to use effective birth control during
             study and for 3 months after receiving study drug.

          -  Must have existing tissue available for correlative studies

        Exclusion Criteria:

          -  No chemotherapy, radiation or surgical resection of malignancy < 3 weeks before start
             of study drug

          -  Prior therapy with other ALK inhibitor investigational agents except crizotinib

          -  Active, uncontrolled, serious infection or medical or psychiatric illness likely to
             interfere with trial

          -  Known HIV infection

          -  Extensive disseminated bilateral interstitial fibrosis or interstitial lung disease,
             (history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia,
             obliterative bronchiolitis or clinically significant radiation pneumonitis) i.e.
             affecting daily living or requiring ongoing therapeutic intervention.

          -  Symptomatic CNS metastases and neurologically unstable or increasing doses of steroids
             < 2 weeks prior to study entry

          -  Major surgery 4 weeks before initiating protocol therapy.

          -  Hypersensitivity to microcrystalline cellulose, mannitol, crospovidone, colloidal
             silicon dioxide, magnesium stearate

          -  Diagnosis or treatment for malignancy other than NHL < 3 years before Day 1 of
             protocol therapy. Exceptions:

               -  Basal or squamous cell carcinoma of the skin

               -  In situ malignancy - completely resected.

               -  Prostate cancer treated with prostatectomy or radiotherapy > 2 years before Day 1
                  of protocol therapy and PSA is undetectable

               -  In situ malignancy - completely resected

          -  Current treatment with another investigational agent < 14 days before enrollment.
             Other non-treatment studies allowed if it won't interfere with study participation.

          -  Myocardial infarction or unstable angina 6 months before enrollment or New York
             Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities.

             o QTcF>450msec

          -  Oral steroids > 4mg dexamethasone or equivalent/day excluding steroids used for
             adrenal insufficiency

          -  Impaired GI function from significant small bowel resection or gastric bypass surgery
             or inability to swallow up to five ceritinib capsules daily

          -  Ongoing GI adverse events > grade 2 (e.g. nausea, vomiting, or diarrhea) at start of
             study.

          -  Receiving medications that meet one of the following criteria and that cannot be
             discontinued at least 1 week prior to start of treatment and for the duration of
             participation:

               -  Medication with a significant known risk of prolonging the QT interval or
                  inducing Torsades de Pointes
                  http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm

               -  Strong inhibitors or strong inducers of CYP3A4/5
                  http://medicine.iupui.edu/flockhart/table.htm or
                  http://www.druginteractioninfo.org

               -  Therapeutic doses of warfarin sodium (Coumadin) or coumadin-derived
                  anti-coagulant.

               -  Enzyme-inducing anticonvulsive agents

               -  Herbal supplements

          -  Pregnant or nursing (lactating) women