Lenalidomide, Bendamustine and Rituximab Induction Therapy for CLL

Trial Purpose and Description

Trial Purpose

The purpose of this research is to evaluate the use of lenalidomide in the treatment of chronic lymphocytic leukemia following completion of standard chemotherapy with bendamustine and rituximab. Lenalidomide is a drug that alters the immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Because of this, researchers believe that it may reduce or prevent the growth of cancer cells. Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM are cancers of the blood. It is currently being tested in a variety of cancer conditions. Its use in this study is considered investigational.

Participation Guidelines

Eligibility Criteria

Inclusion criteria

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.

Exclusion criteria

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.

Sponsor:

Celgene Corporation

Yale Cancer Center

Dates:

March 2012

Last Updated:

January 14, 2013

Study HIC#:

1105008515

Clinicaltrials.gov ID: NCT01465230