HO11415: Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
1. Histologically confirmed CLL/SLL.
2. Understand and voluntarily sign an informed consent document.
3. Age greater than or equal to 18 years at the time of signing the informed consent
4. Subjects must have documented relapsed or refractory CLL/SLL.
- Relapsed disease is defined as progressive disease after achieving a complete or
partial response to the most recent therapy.
- Refractory disease is defined as less than a partial response to the most recent
5. Subjects must have received ≥1 prior chemotherapy regimen for their disease. Prior
therapy with single-agent rituximab does not meet criteria for a prior chemotherapy
regimen (i.e., prior treatment must include cytotoxic chemotherapy agent).
6. In cases of SLL, subjects must have at least one bidimensionally measurable lesion at
least ≥1.5 cm measured in one dimension.
7. Eastern Cooperative Oncology Group performance status of less than or equal to 2 at
8. Laboratory test results within these ranges:
- Absolute neutrophil count greater than or equal to 1500/μL
- Platelet count great than or equal to 100,000/μL
- Subjects with neutrophils <1500/μL or platelets <100,000/μL with splenomegaly or
extensive bone marrow involvement as the etiology for their cytopenias are
- Subjects must have adequate renal function with a creatinine clearance of ≥40
mL/min as determined by the Cockcroft-Gault calculation
- Total bilirubin less than or equal to 2X (times) upper limit laboratory normal
(ULN); subjects with non-clinically significant elevations of bilirubin due to
Gilbert's disease are not required to meet these criteria
- Serum transaminases aspartate aminotransferase (AST) (SGOT) and (alanine
aminotransferase) ALT (SGPT) less than or equal to 5X ULN
- Serum alkaline phosphatase ≤5X ULN
9. Disease-free of prior malignancies for ≥2 years with the exception of basal or
squamous cell skin carcinoma, carcinoma "in situ" of the breast or cervix, or
localized prostate cancer (treated definitively with hormone therapy, radiotherapy,
10. Life expectancy of at least 3 months.
11. All study participants must be willing to be registered into the mandatory RevAssist®
program, and be willing and able to comply with the requirements of RevAssist®.
12. Subjects must not have a known history of hypersensitivity to mannitol.
13. Subjects may have received prior therapy with bendamustine or lenalidomide, but must
not have disease that is refractory to bendamustine or lenalidomide.
14. Prior therapy with rituximab is permitted, even in the setting of
15. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects
intolerant to aspirin may use warfarin or low molecular weight heparin) if clinically
16. Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again
within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be
filled within 7 days as required by RevAssist) and must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control, one highly effective method and one additional effective method AT THE SAME
TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree
to ongoing pregnancy testing. Men must agree to use a latex condom during sexual
contact with a FCBP even if they have had a successful vasectomy. See Appendix:
Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control
Subjects may not have received >5 lines of prior therapy for their disease. Re-treatment
with an identical regimen does not count as a new regimen.
2. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent document or complying with the
3. Pregnant or breast-feeding females. Lactating females must agree not to breast-feed
while taking lenalidomide.
4. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds the
ability to interpret data from the study.
5. Subjects are not eligible if there is a prior history or current evidence of central
nervous system or leptomeningeal involvement.
6. Use of any other experimental drug or therapy within 28 days of enrollment.
7. Known hypersensitivity to thalidomide. 8. The development of erythema nodosum if
characterized by a desquamating rash while taking thalidomide or similar drugs.
9. Disease that is refractory to prior therapy with bendamustine or lenalidomide.
10. Concurrent use of other anti-cancer agents or treatments. 11. Known to be positive
for HIV or infectious hepatitis (type B or C). 12. Prior malignancy, except for
adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast
cancer, or other cancer from which the subject has been disease free for at least 2 years.
13. Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously
exposed to rituximab or other monoclonal antibody therapy.
14. Chronic hepatitis B or hepatitis C infection. 15. New York Heart Association class 3-4