Lenalidomide for the Treatment of CLL Patients With High-Risk Disease
Lenalidomide for the Treatment of CLL Patients With High-Risk Disease
This phase II clinical trial is studying how well lenalidomide works in treating patients with high-risk chronic lymphocytic leukemia. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing.
PRIMARY OBJECTIVES:
I. To determine the time to progression in patients with high-risk chronic lymphocytic leukemia (CLL) treated with lenalidomide.
SECONDARY OBJECTIVES:
I. To determine the clinical response (complete and partial response) in treatment-naïve patients with high-risk CLL treated with single-agent lenalidomide.
II. To determine the incidence of immune-mediated flare reaction. III. To determine the toxicity profile of single-agent lenalidomide in previously untreated patients with high-risk CLL.
IV. To conduct correlative studies in bone marrow, peripheral blood, and/or lymph nodes of patients treated with lenalidomide.
OUTLINE:
Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (by morphological criteria but have persistent minimal residual disease by molecular criteria) or partial response may continue treatment beyond 8 courses. Patients may undergo bone marrow, peripheral blood, and/or lymph node sample collection at baseline and periodically during study for correlative studies.
After completion of study therapy, patients are followed up every 3 months for a maximum of 5 years.
Inclusion Criteria:
Definitive diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
Must have high-risk B-CLL as defined by ≥ one of the following:
Zap-70 and CD38 expression on leukemic cells will not be used as eligibility criteria for enrollment into the clinical trial
No prior treatment for the management of B-CLL
Patients must have B-CLL requiring therapy as defined by the IWCLL criteria
Must have measurable disease meeting one of the following criteria:
No tumor lysis syndrome (TLS) by Cairo-Bishop definition
ECOG performance status 0-2
ANC ≥ 1,500/mm³
Platelet count ≥ 75,000/mm³
Creatinine clearance ≥ 30 mL/min
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN (≤ 5 times ULN if hepatic metastases are present)
Uric acid normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must commit to continued abstinence from heterosexual intercourse or use 2 acceptable methods of contraception (1 highly effective method and 1 additional effective method) ≥ 28 days prior to, during, and for ≥ 28 days after discontinuing lenalidomide
Able to adhere to the study visit schedule and other protocol requirements
No serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
No condition, including the presence of laboratory abnormalities, that would place the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
No known hypersensitivity to thalidomide or lenalidomide
No history of erythema nodosum characterized by a desquamating rash while taking thalidomide or similar drugs
No history of any other cancer except non-melanoma skin cancer or carcinoma in-situ of the cervix or cancer for which the patient is in complete remission and off therapy for > 3 years
No cardiac arrest within the past 6 months
No known history of hepatitis B infection, positive hepatitis B surface antigen, or positive hepatitis C antibody
No other concurrent anti-cancer agents or treatments
More than 28 days since any prior experimental drug or therapy
Aspirin (81 or 325 mg) or warfarin sodium daily as prophylactic anticoagulation required
No prior lenalidomide