Fludarabine (Fludara®) Plus Alemtuzumab (CAMPATH®, MabCampath®) vs Fludarabine Alone in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients

This is a Phase 3, prospective, multicenter, open-label, randomized, controlled study to evaluate and compare the efficacy and safety of fludarabine plus alemtuzumab versus fludarabine alone as second-line therapy for patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Patients who meet all eligibility criteria and sign the informed consent document may be entered on the study.


Eligibility Criteria:
Inclusion Criteria:

* A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National Cancer Institute Working Group (NCI WG) criteria.
* Relapsed or refractory disease after 1 prior regimen except patients who were refractory to (i.e., progressed on) fludarabine or alemtuzumab therapy. Patients who previously responded (complete response or partial response) to fludarabine or alemtuzumab therapy, but who have relapsed at the time of study entry, may be eligible but response to fludarabine or alemtuzumab therapy must have lasted \>12 months (i.e., \>12 months from a documented response to a documented relapse).
* Binet stage A, stage B, or stage C or Rai Stage I through IV disease with evidence of progression as evidenced by the presence of one or more of the following:

I. Evidence of progressive marrow failure as manifested by: 1) a decrease in hemoglobin to \<11g/dL, or 2) a decrease in platelet count to \<100 x 10\^9/L within the previous 6 months, or 3) a decrease in absolute neutrophil count (ANC) to \<1.0 X 10\^9/L.

II. Progressive splenomegaly to \>2 cm below the left costal margin or other organomegaly.

III. Progressive lymphadenopathy.

IV. Progressive lymphocytosis with an increase of 50% over a 2-month period, or an anticipated doubling time of less than 6 months.

* World Health Organization (WHO) performance status (PS) of 0 or 1.
* Life expectancy \>12 weeks.
* Anti-cancer therapy, major surgery, or irradiation was completed \>3 weeks before randomization in this study. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
* Serum creatinine less than or equal to 2.0 x institutional upper limits of normal (ULN) and calculated creatinine clearance (CrCl) greater than or equal to 30mL/min using the Cockroft and Gault formula.
* Adequate liver function as indicated by a total bilirubin, AST, and ALT less than or equal to 2 x the institutional ULN value, unless directly attributable to the patient's tumor.
* Female patients with childbearing potential must have a negative serum pregnancy test with 2 weeks of first dose of study drug(s). Male and female patients must agree to use an effective contraceptive method while on study treatment, if appropriate, and for a minimum of 6 months following study therapy.
* Signed, written informed consent.

Exclusion Criteria:

* Previously treated with \>1 prior regimen for B-CLL.
* Previously treated with a fludarabine plus alemtuzumab (FluCAM) regimen for B-CLL.
* Positive Coombs test and actively hemolyzing.
* Absolute neutrophil count (ANC) \<1.5 x 10\^9/L or platelet count \<75 x 10\^9/L, unless due to bone marrow involvement.
* Medical condition requiring chronic use of pharmacologic doses of oral corticosteroids, i.e. anything other than replacement dose levels.
* History of anaphylaxis following exposure to monoclonal antibodies.
* Use of investigational agents within 6 weeks prior to study randomization.
* Active infection or history of severe infection (grade 4) within 3 months prior to study randomization.
* Known to be human immunodeficiency virus (HIV) positive.
* Autoimmune thrombocytopenia.
* Active second malignancy.
* Known central nervous system (CNS) involvement with B-CLL.
* Other severe, concurrent diseases, including tuberculosis, mental disorders, serious cardiac functional capacity (Class III or IV as defined by the New York Heart Association Classification), severe diabetes, severe hypertension, pulmonary disease (chronic obstructive pulmonary disease \[COPD\] with hypoxemia), or major organ malfunction (liver, kidney) that could interfere with the patient's ability to participate in the study.
* Pregnant or nursing women.
* Patients that have progressed with more aggressive B-cell cancers such as Richter's syndrome.
* Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive hepatitis B serologies without prior immunization.