Clinical trial NCT00500058 (phase 1, status: completed)
Conditions: lymphoma, non-hodgkin
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: sb-485232, rituximab
SMILES: ClCCN(CCCl)P1(=O)NCCCO1
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of any subtype of CD20+ B cell NHL. Subjects must
             have disease that progressed after standard therapy or for which there is no effective
             standard therapy (including high-dose therapy and autologous stem cell
             transplantation). NOTE: If the subject has had a prior autologous stem cell
             transplant, it must have occurred at least three months prior to screening and the
             subject must be fully recovered from any acute toxicities.

          -  Prior treatment with Rituximab is allowed, provided it was completed at least six
             months before study enrollment.

          -  Male or female ≥ 18 years of age.

          -  Measurable or evaluable disease.

          -  Predicted life expectancy of at least 12 weeks.

          -  ECOG Performance Status of 0 or 1.

          -  No chemotherapy, immunotherapy, hormonal therapy, or biological therapy for cancer,
             radiotherapy, or surgical procedures (except for minor surgical procedures) within
             four weeks before beginning treatment with SB-485232 (6 weeks for nitrosoureas and
             mitomycin C). Subjects must have recovered from toxicities (incurred as a result of
             previous therapy) sufficiently to be entered into a Phase I study.

          -  A signed and dated written informed consent form is obtained from the subject.

          -  The subject is able to understand and comply with protocol requirements, timetables,
             instructions and protocol-stated restrictions.

        The subject is likely to maintain good venous blood access for PK and PD sampling
        throughout the study.

          -  A female is eligible to enter and participate in the study if she is of:

             a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant)
             including any female who:

          -  has had a hysterectomy,

          -  has had a bilateral oophorectomy (ovariectomy),

          -  has had a bilateral tubal ligation,

          -  is post-menopausal (demonstrate total cessation of menses for greater than 1year), If
             amenorrheic for less than one year, post-menopausal status will be confirmed by serum
             follicle stimulating hormone (FSH) and oestradiol concentrations at screening. or, b.
             childbearing potential, has a negative serum pregnancy test at the Screen Visit, and
             agrees to one of the following GSK acceptable contraceptive methods:

          -  any intrauterine device (IUD) with a documented failure rate of less than

             1% per year.

          -  vasectomized partner who is sterile prior to the female subject's entry and is the
             sole sexual partner for that female.

          -  oral contraceptive (either combined or progesterone only).

          -  because of the unacceptable failure rate of barrier (chemical and/or physical)
             methods, the barrier method of contraception must only be used in combination with
             other acceptable methods described above.

          -  Adequate organ function,

        Exclusion Criteria:

          -  Women who are pregnant or are breast-feeding.

          -  Significant cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal or
             autoimmune conditions that in the opinion of the investigator and/or GSK medical
             monitor, places the subject at an unacceptable risk as participant in this trial.

          -  The subject has diabetes mellitus with poor glycemic control.

          -  The subject has a history of human immunodeficiency virus (HIV) or other
             immunodeficiency disease.

          -  The subject has positive Hepatitis B surface antigen.

          -  Corrected QT interval (QTc) > 480msec.

          -  The subject has a history of a severe infusion related reaction or tumor lysis
             syndrome following treatment with Rituximab (Section 10.2.2).

          -  The subject has a circulating malignant cell count > 25,000/mm3 in peripheral blood.

          -  The subject has known anaphylaxis or IgE-mediated hypersensitivity to murine proteins.

          -  The subject has an acute infection or severe or uncontrolled infections requiring
             systemic antibiotic therapy.

          -  Any serious medical or psychiatric disorder that would interfere with subject safety
             or informed consent.

          -  Known leptomeningeal disease or evidence of prior or current metastatic brain disease.
             Routine screening with central nervous system (CNS) imaging studies (CT or MRI) is
             required only if clinically indicated.

          -  Receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational
             therapy.

          -  Oral corticosteroids within 14 days of study entry.

          -  History of alcohol abuse within six months of screening or alcohol consumption in the
             past six months exceeding seven drinks/week for women and 14 drinks/week for men
             (where 1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).

          -  History of ventricular arrhythmias requiring drug or device therapy.

          -  Any unresolved or unstable serious toxicity from prior administration of another
             investigational drug.

          -  Any investigational drug within 30 days or five half-lives (whichever is longer)
             preceding the first dose of SB-485232.

          -  Donation of blood in excess of 500 mL within a 56-day period prior to dosing.