
    poor accrual
  
['lymphoma']
['tak228']

        Inclusion Criteria:

          1. Each patient must meet all of the following inclusion criteria to be enrolled in the
             study: 1. Male or female patients 18 years or older.

          2. Voluntary written consent must be given before performance of any study related
             procedure not part of standard medical care, with the understanding that consent may
             be withdrawn by the patient at any time without prejudice to future medical care.

          3. Female patients who: are postmenopausal for at least 1 year before the screening
             visit, OR are surgically sterile, OR if they are of childbearing potential, agree to
             practice 1 effective methods of contraception and one additional effective (barrier)
             method, at the same time, from the time of signing the informed consent through 90
             days (or longer, as mandated bu local labeling [eg,USPI, SmPC, etc;]) after the last
             dose of study drug, or agree to practice true abstinence, when this is in line with
             the preferred and usual lifestyle of the patient (Periodic abstinence [e.g, calendar,
             ovulation, symptothermal, postovulation methods] and withdrawal,spermicides only, ad
             lactational amenorrhea are not acceptable methods of contraception.Female and male
             condoms should not be used together.

          4. Male patients, even if surgically sterilized (ie, status post-vasectomy), who: agree
             to practice highly effective barrier contraception during the entire study treatment
             period and through 120 days after the last dose of study drug, or agree to practice
             true abstinence, when this is in line with the preferred and usual lifestyle of the
             patient (Periodic abstinence [e.g, calendar, ovulation, symptothermal, postovulation
             methods for the female partner] and withdrawal, spermicides only, ad lactational
             amenorrhea are not acceptable methods of contraception. Female and male condoms should
             not be used together; Agree not to donate sperm during the course of this study or 120
             days after receiving their last dose of study drug

          5. Patients must have a diagnosis of prior treated diffuse large b-cell lymphoma, mantle
             cell lymphoma, transformed lymphoma, follicular lymphoma (any grade), small
             lymphocytic lymphoma, marginal zone lymphoma, or Hodgkin lymphoma with at least 2
             lines of therapy without a curative treatment options.

          6. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance
             status </= 2.

          7. Adequate organ function, as specified below, within 3 weeks before the first dose of
             study drug: a) Bone marrow reserve consistent with: absolute neutrophil count (ANC)
             >/=1.5 x 10^9/L; platelet count >/=100 x 10^9/L; hemoglobin >/=9 g/dL without
             transfusion within 1 week preceding study drug administration; b) Hepatic: total
             bilirubin < /=1.5 x upper limit of normal (ULN), transaminases (aspartate
             aminotransferase-AST and alanine aminotransferase ALT) </= 2.5 x ULN (</= 5 x ULN if
             liver metastases are present); c) Renal: creatinine clearance >/= 50 mL/min based
             either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour); d)
             Metabolic: fasting serum glucose (</=130 mg/dL) and fasting triglycerides </=300
             mg/dL;

          8. Ability to swallow oral medications;

          9. Measurable disease, defined as >/=1.5 cm on imaging assessment.

        Exclusion Criteria:

          1. Eligible for therapy for the lymphoid malignancy which has a high likelihood of a
             curative result in the opinion of the investigator.

          2. Female patients who are both lactating and breastfeeding or have a positive serum
             pregnancy test during the screening period

          3. Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol

          4. Concurrent malignancies except basal or squamous cell carcinoma of the skin, or
             cervical carcinoma in situ treated with curative intent. Any cancer from which the
             patient has been disease free for at least 2 years is permissible.

          5. Treatment with any investigational products within 14 days before the first dose of
             study drug

          6. Failed to recover to baseline or stable grade 1 from the reversible effects of prior
             anticancer therapies with the exception of alopecia.

          7. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI
             disease, or for an unknown reason that may alter the absorption of TAK228; such as
             significant chronic diarrhea. In addition, patients with enteric stomata are also
             excluded.

          8. Poorly controlled diabetes mellitus defined as HbA1c > 7%; subjects with a history of
             transient glucose intolerance due to corticosteroid administration are allowed in this
             study if all other inclusion/exclusion criteria are met;

          9. History of any of the following within the last 6 months prior to study entry:
             ischemic myocardial event, including angina requiring therapy and artery
             revascularization procedures; Ischemic cerebrovascular event, including TIA and artery
             revascularization procedures; Requirement for inotropic support (excluding digoxin) or
             serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation,
             ventricular fibrillation or ventricular tachycardia); Placement of a pacemaker for
             control of rhythm; New York Heart Association (NYHA) Class III or IV heart failure;
             Pulmonary embolism.

         10. History of any of the following within the last 6 months prior to study entry:
             Requirement of inotropic support; Serious uncontrolled cardiac arrhythmia (including
             atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia);
             Placement of a pacemaker for control of rhythm

         11. Significant active cardiovascular or pulmonary disease at the time of study entry,
             including: uncontrolled high blood pressure (i.e., systolic blood pressure >180 mm Hg,
             diastolic blood pressure > 95 mm Hg) Use of anti-hypertensive agents to control
             hypertension before cycle 1 day 1 is allowed; Pulmonary hypertension; Uncontrolled
             asthma or O2 saturation < 90% by ABG (Arterial Blood Gas) analysis or pulse oximetry
             on room air; Significant valvular disease; severe regurgitation or stenosis by imaging
             independent of symptom control with medical intervention, or history of valve
             replacement; medically significant (symptomatic) bradycardia; History of arrhythmia
             requiring an implantable cardiac defibrillator; Baseline prolongation of the
             rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480
             milliseconds, or history of congenital long QT syndrome, or torsades de pointes).

         12. Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C9
             or CYP2C19 within 1 week preceding the first dose of study drug.

         13. Patients receiving systemic corticosteroids (either IV or oral steroids, excluding
             inhalers or low-dose hormone replacement therapy as defined no greater than 20mg of
             prednisone daily) within 1 week before administration of the first dose of study drug.

         14. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease,
             active central nervous system disease, active infection, or any other condition that
             could compromise participation of the patient in the study.

         15. Central nervous system (CNS) lymphoma.

         16. Known human immunodeficiency virus infection.

         17. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
             infection.

         18. Diagnosed or treated for another malignancy within 2 years before administration of
             the first dose of study drug, or previously diagnosed with another malignancy and have
             any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma
             in situ of any type are not excluded if they have undergone complete resection

         19. Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within
             7 days before receiving the first dose of study drug
      