Clinical trial NCT02471391 (phase 2, status: unknown status)
Conditions: mantle cell lymphoma
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: abt-199, ibrutinib
SMILES: CC1(C)CCC(CN2CCN(CC2)C2=CC=C(C(=O)NS(=O)(=O)C3=CC=C(NCC4CCOCC4)C(=C3)[N+]([O-])=O)C(OC3=CN=C4NC=CC4=C3)=C2)=C(C1)C1=CC=C(Cl)C=C1, NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1
Eligibility criteria:

        Inclusion Criteria:

          1. Subject must be >/= 18 years of age.

          2. Subject must have a confirmed diagnosis of Mantle Cell Lymphoma (MCL) according to WHO
             (2008) criteria, and have received at least one prior line of systemic therapy for
             MCL.

          3. Subject requires treatment in the opinion of the investigator, and has at least one
             site of radiographically assessable disease not previously irradiated (lymph node with
             largest diameter >/= 1.5cm, or unequivocal hepatomegaly / splenomegaly)

          4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of </= 2.

          5. Subject must have adequate bone marrow function at Screening as follows:

               -  Absolute Neutrophil Count (ANC) >/= 1.0 x 109/L (neutropenia due to marrow
                  infiltration may be supported by growth factors);

               -  Platelets >/= 50 x 109/L (entry platelet count must be independent of transfusion
                  within 7 days).

          6. Subject must have adequate coagulation, renal, and hepatic function, per laboratory
             reference range at Screening as follows:

               -  aPTT and PT not to exceed 1.5 × the upper limit of normal (ULN);

               -  Serum creatinine not to exceed 2 x ULN, and a calculated creatinine clearance of
                  at least 50 mL/min using the Cockcroft-Gault equation or a 24-hour urine
                  collection;

               -  AST or ALT </= 3.0 × the upper normal limit (ULN) of institution's normal range;
                  Bilirubin </= 1.5 × ULN. Subjects with documented Gilbert's Syndrome may have a
                  bilirubin > 1.5 × ULN.

          7. Female subjects of childbearing potential and non-sterile male subjects (with partners
             of child bearing potential) must practice at least one of the following methods of
             birth control with partner(s) from initial study drug administration to 90 days after
             the last dose of study drug:

               -  Total abstinence from sexual intercourse as the preferred life style of the
                  subject; periodic abstinence is not acceptable;

               -  Surgically sterile partner(s); acceptable sterility surgeries are: vasectomy,
                  bilateral tubal ligation, bilateral oophorectomy or hysterectomy;

               -  Intrauterine device (IUD);

               -  Double-barrier method (contraceptive sponge, diaphragm or cervical cap with
                  spermicidal jellies or cream AND a condom);

               -  Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months
                  prior to study drug administration.

          8. Female subjects of childbearing potential must have a negative serum (beta-human
             chorionic gonadotropin [B-hCG]) or urine pregnancy test at Screening. Women who are
             pregnant or breastfeeding are ineligible for this study

          9. Male subjects must agree to refrain from sperm donation, from initial study drug
             administration until 90 days after the last dose of study drug.

         10. Subject is able to swallow whole tablets.

         11. Subject (or their legally-acceptable representatives) must sign an informed consent
             document indicating that they understand the purpose of and procedures required for
             the study, including biomarkers, and are willing to participate in the study.

        Exclusion Criteria:

          1. Subject has undergone an allogeneic stem cell transplant within the last 6 months or
             currently has active graft-vs-host disease requiring the use of immunosuppressants.

          2. Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks), including
             autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP).

          3. Subject has known central nervous system involvement by MCL.

          4. Subject previously participated in an ibrutinib clinical trial or subject previously
             received a Bruton's tyrosine kinase (BTK) inhibitor other than ibrutinib

          5. Subject has received the following within 30 days prior to the first dose of study
             drug:

             •Monoclonal antibody given with anti-neoplastic intent.

          6. Subject has received any of the following within 14 days prior to the first dose of
             study drug, or has not recovered to less than CTC grade 2 clinically significant
             adverse effect(s)/toxicity(s) of the previous therapy:

               -  Any anti-cancer therapy including chemotherapy, or radiotherapy;

               -  Investigational therapy, including targeted small molecule agents.

          7. Subject has received the following within 7 days prior to the first dose of study
             drug:

             •Steroid therapy given with anti-neoplastic intent

          8. Subjects requires ongoing therapy with:

               -  Potent CYP3A inhibitors (such as indinavir, ketoconazole, and clarithromycin),

               -  Potent CYP3A inducers (e.g., rifampin, phenytoin, carbamazepine or St. John's
                  Wort),

               -  Warfarin, or or equivalent vitamin K antagonist (eg, phenprocoumon),

               -  Antiretroviral medications.

          9. Subject has consumed the following within 3 days prior to the first dose of study
             drug.

               -  Grapefruit, or

               -  Grapefruit products, or

               -  Seville oranges (including marmalade containing Seville oranges), or

               -  Star fruit

         10. Subject has clinically significant cardiovascular disease such as uncontrolled or
             symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6
             months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as
             defined by the New York Heart Association Functional Classification.

         11. Subject has a life-threatening illness, medical condition, or organ system dysfunction
             which, in the investigator's opinion, could compromise the subject's safety, interfere
             with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at
             undue risk.

             •specifically, a subject with history of stroke or intracranial hemorrhage within 6
             months prior to enrollment is excluded

         12. Subject has a history of other active malignancies other than MCL within the past 2
             years prior to study entry, with the exception of:

               -  Adequately treated in situ carcinoma of the cervix uteri,

               -  Adequately treated basal cell carcinoma of the skin or localized squamous cell
                  carcinoma of the skin,

               -  Previous malignancy confined and surgically resected (or treated with other
                  modalities) with curative intent.

         13. Subject has known history of human immunodeficiency virus (HIV) or active Hepatitis C
             Virus or active Hepatitis B Virus infection or any uncontrolled active systemic
             infection requiring intravenous (IV) antibiotics.

         14. Received live, attenuated vaccines within 4 weeks of first dose of ibrutinib

         15. Major surgery within 4 weeks of first dose of ibrutinib