Rituximab in Pretreated Elderly or Unfit B-CLL Patients

Study of Rituximab in Addition to Glucocorticoid in Pretreated Elderly or Unfit Patients With Chronic B Lymphocytic Leukemia

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.