subcutaneous alemtuzumab (campath®, mabcampath®) in relapsed/refractory b-cell chronic lymphocytic leukemia

Conditions: B-Cell Chronic Lymphocytic Leukemia (B-CLL)

Summary: this is a phase ii, open-label, prospective, multicenter study to evaluate the efficacy and safety of subcutaneously administered alemtuzumab (campath, mabcampath) as therapy for patients with relapsed or refractory b-cll who have been previously treated.


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. * world health organization (who) performance status of 0, 1, or 2. * life expectancy ≥ 12 weeks. * previous therapy with at least one but no more than 5 regimens (single agent or combination regimen). one therapy regimen is defined as consecutive, contiguous cycles of the same drug(s) with no treatment interruptions lasting \> 3 months. * patient requires treatment for cll per the following criteria: -rai stage iii or iv; -rai stage 0-ii with at least one of the following - evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia; massive (i.e. greater than 6 cm below the left costal margin) or progressive splenomegaly; progressive lymphocytosis with an increase of greater than 50% over a 2-month period or an anticipated doubling time of less than 6 months; lymphocyte count \> 100\*10\^9/l; b symptoms. * more than 3 weeks since prior chemotherapy. patient must have recovered from the acute side effects incurred as a result of previous therapy. * more than 3 weeks since using investigational agents. patient must have recovered from the acute side effects incurred as a result of previous therapy. * serum creatinine and conjugated (direct) bilirubin less than or equal to 2 times the institutional upper limit of normal (uln) unless secondary to direct infiltration of the liver with cll. * female patients with childbearing potential must have a negative pregnancy test (serum or urine) within 2 weeks of first dose of study drug(s). all 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 (in the us, includes the health insurance portability and accountability act of 1996 (hipaa) authorization) exclusion criteria: * positive coombs test and evidence of active hemolysis. * platelet count less than 50\*10\^9/l without splenomegaly. * history of anaphylaxis following exposure to rat or mouse derived cdr-grafted humanized monoclonal antibodies. * previously treated with campath. * previous bone marrow transplant. * known central nervous system (cns) involvement with b-cll * active infection, including human immunodeficiency virus (hiv) positive. * active second malignancy. * recent documented history (within 2 years) of active tuberculosis (tb), current active tb infection, currently receiving anti-tuberculous medication (e.g., inh, rifampin, streptomycin, pyrazinamide, or others). * active hepatitis or a history of prior viral hepatitis b or hepatitis c, or positive hepatitis b serologies. patients with a positive hepatitis b surface antibody (hbsab) test with a documented history of prior hepatitis b immunization are eligible as long as other criteria are met (i.e. negative tests for: hepatitis b surface antigen (hbsag), hepatitis b core antibody (hbcab) and hepatitis c virus antibody (hcvab)). * other severe, concurrent diseases (e.g., cardiac or pulmonary disease), mental disorders, or major organ malfunction (liver, kidney) that could interfere with the patient ability to participate in the study. * pregnant or nursing women. * cytomegalovirus (cmv) positive by polymerase chain reaction (pcr) (above the level of detection). a patient that is pcr positive will require treatment to reduce the viral load to a non-detectable level; but such a patient may be considered for study entry once the infection has been treated. * medical condition requiring chronic use of oral corticosteroids at a dose higher than physiologic replacement.

Keywords: campath alemtuzumab leukemia mabcampath chronic subcutaneous cll c-cll relapsed refractory chronic lymphocytic leukemia