A Phase III Study to Evaluate the Efficacy and Safety of Front-Line Therapy With Alemtuzumab (Campath, MabCampath) vs Chlorambucil in Patients With Progressive B-Cell Chronic Lymphocytic Leukemia
- Histopathologically confirmed diagnosis of B-CLL with CD5, CD19, or CD23 positive
- Rai Stage I through IV disease with evidence of progression as evidenced by the
presence of one or more of the following:1. Disease-related B symptoms (fever of
greater than 38 celsius (100.5 F) for greater than or equal to 2 weeks without
evidence of infection, night sweats without evidence of infection, weight loss >10%
within previous 6 months. 2. Evidence of progression marrow failure as manifested by:
a. decrease in hemoglobin to <11g/dL or b. decrease in platelet count to <100x10 to
the ninth/L within the previous 6 months or c. decrease in absolute neutrophil count
(ANC) to <1.0x10 to the ninth/L within the previous 6 months. 3. Progressive
splenomegaly to >2 cm below the left costal margin or other organomegaly with
progressive increase over 2 consecutive clinic visits greater than or equal to 2
weeks apart. 4. Progressive lymphadenopathy with at least 5 sites of involvement with
either two nodes at least 2cm in longest diameter or one node greater than or equal
to 5cm in longest diameter with progressive increase over 2 consecutive visits
greater than or equal to weeks apart. 5. Progressive lymphocytes with an increase of
>50% over a 2-month period, or an anticipated doubling time of less than 6 months.
- Received no previous chemotherapy for B-CLL.
- Life expectancy of at least 12 weeks.
- WHO performance status of 0, 1, or 2.
- Serum creatinine less or equal to 2.0 times the institutional upper limit of normal
- Adequate liver function as indicated by a total bilirubin, AST, and ALT less or equal
to 2 times the institutional ULN value, unless directly attributable to the disease.
- Female patients with childbearing potential must have a negative serum pregnancy test
within 2 weeks prior to randomization. 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 after study therapy.
- Signed, written informed consent.
- 18 years of age or older.
- ANC less than 500 million per liter or platelet count less than 10 billion per liter.
- Medical condition requiring chronic use of oral corticosteroids.
- Autoimmune thrombocytopenia.
- Previous bone marrow transplant.
- Use of investigational agents within previous 30 days.
- Positive for HIV.
- Past history of anaphylaxis following exposure to rat or mouse-derived complementary
determining region (CDR) grafted humanized monoclonal antibodies.
- Active infection.
- Serious cardiac or pulmonary disease that could interfere with their ability to
participate in the study.
- Recent documented (with in 2 years) of active tuberculosis (TB), current active TB,
or currently receiving anti-tuberculosis medication.
- Active secondary malignancy.
- Central nervous system involvement with CLL.
- Positive quantitative CMV by PCR assay (using the laboratory normal ranges).
- A diagnosis of mantle cell lymphoma.
- Other severe, concurrent diseases or mental disorders.
- Pregnant or lactating women.