Maintenance Therapy with Lenalidomide Following Bendamustine and Rituximab Induction Therapy for Chronic Lymphocytic Leukemia
Trial Purpose and Description
The primary objective of the study will be to determine if maintenance therapy with Lenalidomide improves response rates following induction therapy with Bendamustine/Rituximab.
Secondary Objective: The secondary objective of the study will be to evaluate for toxicities related to the maintenance therapy.
The study will be a single institution nonrandomized phase II study. Patients with a diagnosis of CLL based on NCI criteria that have completed induction chemotherapy with six cycles of bendamustine 90mg/m2 on days 1 and 2 and rituximab 375mg/m2 (BR) on day 1 every 28 days will be eligible for the study. Please see section 5.2 on patient screening and eligibility for additional inclusion and exclusion criteria. The induction therapy may be done by the patient’s primary oncologist or at Smilow Cancer Hospital at Yale. Response to induction therapy in order to determine complete response (CR), partial response (PR), and stable disease will be determined by flow cytometry and cytogenetics three months following completion of BR. Patients with stable disease or those who have achieved a partial response three months after completion of the induction therapy will go on to receive maintenance therapy with single agent Lenalidomide. Patients may start the maintenance therapy up to six months after completion of the induction therapy. Prior to enrollment in the study each patient will have a complete blood count, immunophenotyping of peripheral blood lymphocytes, comprehensive metabolic panel, quantitative immunoglobulins, and bone marrow with flow cytometry and cytogenetics (bone marrow-optional). Please see section 2 for the schedule of study assessments. The Lenalidomide will start at a dose of 5mg daily on days 1-21 every 28 days. If the patient tolerates the dose of 5mg for the first cycle, the dose will be increased to 10mg at the start of cycle 2. Therapy will continue for 12 cycles in the absence of disease progression or unacceptable toxicities. Patients will be assessed prior to each cycle of Lenalidomide for toxicity via clinical examination and laboratory analysis. Flow cytometry of the peripheral blood will be
monitored every three months. Response will be assessed using the NCI working group guidelines for complete response, partial response, stable disease, and progressive disease.
- 18 Years - 90 Years
1. Understand and voluntarily sign an informed consent form.
2. Age ≥18 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. CLL as diagnosed by NCI criteria who require treatment
5. All previouscancer therapy, including radiation,hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.
6. ECOG performance status of ≤ 2 at studyentry (see Appendix).
7. Laboratory test results within these ranges:
•Absolute neutrophil count ≥ /mm³ 1000
•Platelet count ≥ /mm³ 70,000
Renal function assessed by calculated creatinine clearance as follows (see
Appendix: Cockcroft-Gault estimation of CrCl):
1. Phase II subjects must have calculated creatinine c≥learance
30ml/min by Cockcroft-Gault formula. See section below, “Dosing Regimen”, regarding lenalidomide dose adjustment for calculated creatinine clearance ≥ 30ml/min and < 60ml/min.
•Total bilirubin ≤ 1.5 x ULN
•AST (SGOT) and ALT (SGPT) ≤ 3 x ULN.
8. Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma “insitu” of the cervix or breast.
9. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements ofRevAssist®.
10. 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) 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 effectivemethod 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 Methods.
11. Able to take aspirin (81 or 325 mg) daily asprophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
12. Completed induction chemotherapy with Bendamustine90mg/m2 days 1-2 and rituximab 375mg/m2 day 1 every 28 days for 6 cycles.
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
3. 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 thestudy.
4. Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome (see Appendix). Subjects maybe enrolled upon correction of electrolyte abnormalities.
5. Use of any other experimental drug or therapy within 28 days of baseline.
6. Known hypersensitivity to thalidomide.
7. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomideor similar drugs.
8. Any prior use of lenalidomide.
9. Concurrent useof other anti-cancer agents or treatments.
10. Known seropositive for or active viral infection with human immunodeficiency virus (HIC), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
- Celgene Corporation
- Yale Cancer Center
- March 2012
- Last Updated:
- January 14, 2013
- Study HIC#:
Clinicaltrials.gov ID: NCT01465230