Rituximab in Pretreated Elderly or Unfit B-CLL Patients
Rituximab in Pretreated Elderly or Unfit B-CLL Patients
The study will test the efficacy rituximab in addition to glucocorticoids for the treatment
 of B-CLL in elderly or unfit patients.
Patient Population: Pretreated patients with symptomatic B-CLL 18-64 years of age with poor
 performance status or >/=65 years of age with any performance status.

 Treatment: Up-to 4 cycles of glucocorticoid (Methylprednisolone or Dexamethasone) and
 Rituximab every 21 day.

 Study Duration: The study period for each subject is expected to be 21 months. Subjects will
 receive up-to 4 cycles of IV infusion of Rituximab and Glucocorticoid. Maximum duration of
 treatment is expected to be 6 months. Subjects will complete scheduled visits not later than
 Study Month 21, thereafter they will enter into the long-term follow-up period. Subjects will
 be followed every 3 months for disease progression, initiation of subsequent leukemia
 treatment or survival.
Inclusion Criteria:

 -  The diagnosis of CD20 positive chronic B lymphocytic leukemia (BCLL) confirmed by
 biopsy or flow-cytometry.

 -  Previously treated patients with stage Rai I-IV and progressive disease (according to
 IWCLL 2008 guidelines).

 Active B-CLL is defined by at least one of the following:

 At least one of the disease related symptoms:

 -  Constitutional symptoms:

 -  Weight loss >10% within the previous 6 months;

 -  Fatigue (e.g., WHO performance status >/=2);

 -  Fever >/=38C >/=2 weeks without evidence of infection;

 -  Night sweats for more than 1 month without evidence of infection.

 -  Evidence of progressive marrow failure as manifested by development of, or worsening
 of, anemia and/or thrombocytopenia

 -  Autoimmune hemolysis and/or thrombocytopenia poorly responsive to corticosteroid
 therapy.

 -  Massive (i.e., >/=6 cm bellow left costal margin) or progressive or symptomatic
 splenomegaly.

 -  Massive lymphadenopathy or conglomerates (i.e., >/=10 cm in largest diameter) or
 progressive or symptomatic lymphadenopathy.

 -  Progressive lymphocytosis with an increase >50% over a 2-month period or an
 anticipated doubling time of less than 6 months. In patients with initial blood
 lymphocyte counts of less than 30x10^9/L LDT should not be used as a single parameter
 to define treatment indication. Marked hypogammaglobulinemia or the development of a
 monoclonal protein in the absence of any of the above criteria for active disease is
 not sufficient for protocol therapy.

 -  Either of the following:

 -  18 years of age or older with impaired performance status (CIRS > 6) and /or

 -  65 years of age or older with any performance status.

 -  Signed informed consent form.

 Exclusion Criteria:

 -  Intolerance to exogenous protein or known severe reaction to the administration of
 Rituximab.

 -  Active infection.

 -  Cancer radiotherapy, biological therapy or chemotherapy within 3 weeks prior to Study
 Day 1.

 -  TBC or fungal infection within the past 6 months even if adequately controlled by
 treatment.

 -  Severe organ deficiency preventing the participation in the study.

 -  Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1.

 -  Active peptic ulcer.

 -  Inadequately controlled diabetes mellitus.

 -  Suspected or confirmed B-CLL CNS disease.

 -  Known to be HIV positive.

 -  Difficult to control, uncooperative patients.

 -  Allergic disorders in need of chronic glucocorticoid therapy.

 -  Other oncological diseases requiring active treatment (except hormonal therapy).

 -  Pregnancy and breastfeeding.

 -  Patients of reproductive potential who are not using effective methods of
 contraception.