Bendamustine and Rituximab Induction Therapy and Maintenance Rituximab and Lenalidomide in Previously Untreated CLL/SLL

• Status: Active, not recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The investigators propose a treatment strategy where patients are treated with induction chemoimmunotherapy consisting of rituximab + bendamustine for 6 cycles, followed by initiation of maintenance rituximab and lenalidomide among patients achieving an objective response (i.e., at least stable disease with some tumor shrinkage) to induction therapy. The goal of maintenance therapy will be to capitalize on the cytoreduction following induction chemotherapy with a maintenance regimen that has also shown promising activity in CLL, in order to allow for improved PFS in this population.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Wisconsin, Madison
• Collaborators: Celgene Corporation; Genentech, Inc.
• Treatments: Bendamustine Hydrochloride; Lenalidomide; Rituximab; Thalidomide

Criteria

Inclusion Criteria:

• Histologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)

• No prior cytotoxic chemotherapy for their disease; prior therapy with single-agent rituximab is permitted

• Understand and voluntarily sign an informed consent document

• In cases of SLL, subjects must have at least one bidimensionally measurable lesion at least >= 1.5 cm measured in one dimension

• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry

• Absolute neutrophil count >= 1500/uL

• Platelet count >= 100,000/uL

• Subjects with neutrophils < 1500/uL or platelets < 100,000/uL with splenomegaly or extensive bone marrow involvement as the etiology for their cytopenias are eligible

• Subjects must have adequate renal function with a creatinine clearance of >= 40 mL/min as determined by the Cockcroft-Gault calculation

• Total bilirubin =< 2 x 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) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x ULN

• Serum alkaline phosphatase =< 5 x ULN

• 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, or surgery)

• Life expectancy of at least 3 months

• All study participants must be willing to be registered into the mandatory Revlimid REMS program after completion of induction chemoimmunotherapy and prior to maintenance therapy, and be willing and able to comply with the requirements of the Revlimid REMS program

• Subjects must not have a known history of hypersensitivity to mannitol

• Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease

• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program

• 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 indicated

• 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 the Revlimid REMS® program) 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

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document or complying with the protocol treatment

• Pregnant or breast-feeding females; lactating females must agree not to breast-feed while taking lenalidomide

• 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

• Subjects are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement

• Known hypersensitivity to thalidomide

• Concurrent use of other anti-cancer agents or treatments

• Known to be positive for human immunodeficiency virus (HIV) or infectious hepatitis (type B or C)

• 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

• Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously exposed to rituximab or other monoclonal antibody therapy

• Chronic hepatitis B or hepatitis C infection

• New York Heart Association class 3-4 heart failure

• More than one grade 2 or higher transaminase elevation