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.

Eligibility Criteria:
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.