Pentostatin, Cyclophosphamide, and Rituximab Followed By Campath-1H in Patients With Relapsed or Refractory B-Cell CLL

Inclusion criteria:

Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria:

Peripheral blood absolute lymphocyte count greater than 5,000/mm^3
Lymphocytosis must comprise small to moderate size lymphocytes with no greater than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically

Phenotypically characterized CLL defined by the following:

Predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-cell markers (CD3 or CD2)
B cell expresses either kappa or lambda light chains
Surface immunoglobulin with low cell surface density expression

Requires chemotherapy, as indicated by any of the following:

Disease-related symptoms

Weight loss of 10% or more within the past 6 months
Extreme fatigue
Fevers greater than 100.5°F for 2 weeks without evidence of infection
Night sweats without evidence of infection
Evidence of progressive marrow failure manifested by the development of or worsening anemia (hemoglobin no greater than 10 g/dL) and/or thrombocytopenia (platelet count no greater than 100,000/mm^3)
Massive (i.e., greater than 6 cm below left costal margin) or progressive splenomegaly
Massive nodes or clusters (i.e., greater than 10 cm in longest diameter) or progressive adenopathy
Progressive lymphocytosis with an increase of greater than 50% over a 2-month period OR an anticipated doubling time of less than 6 months

Demonstrated progression after at least 1 course of either an alkylating agent-based or purine nucleoside-based (e.g., fludarabine) regimen OR failed to achieve a meaningful response OR relapsed after prior therapy

Patients who have relapsed after a pentostatin-based regimen are eligible provided the response was greater than 12 months prior to study entry
18 and over
ECOG Performance Status 0-2
Bilirubin no greater than 2 mg/dL (unless secondary to tumor, hemolysis, or Gilbert syndrome)
Creatinine no greater than 2.0 mg/dL
Creatinine clearance ≥ 30 mL/min
Negative pregnancy test
Fertile patients must use 2 methods of effective contraception (including 1 barrier method) for at least 28 days before starting lenalidomide, while participating in the study, and for at least 28 days after discontinuation/stopping lenalidomide
At least 8 weeks since prior rituximab
At least 6 weeks since prior chemotherapy

At least 1 year since prior pentostatin, cyclophosphamide, and rituximab (PCR) therapy

PCR therapy at least 1 year prior to study entry allowed

Exclusion criteria:

Bone marrow dysplasia related to prior therapy
New York Heart Association class III or IV heart failure
Prior lenalidomide
Other malignancy within the past 2 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
Pregnant or nursing
Concurrent oral or IV antibiotics for active infection