Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial)
Condition: B-Cell Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Lenalidomide; Chlorambucil
Intervention description: For patients with normal renal function (defined as CrCl ≥ 60 mL/min), 5 mg once daily on Days 1 through 28 of the first 28-day cycle, 10 mg once daily on Days 1 through 28 starting at the second cycle, 15 mg once daily starting at the third cycle and for the remainder of the study until PD or unacceptable toxicity, whichever occurs first.
For patients with moderate renal impairment (defined as CrCl ≥ 30 to < 60 mL/min), 2.5 mg once daily on Days 1 through 28 of the first 28-day cycle, 5 mg once daily on Days 1 through 28 starting at the second cycle, 7.5 mg once daily starting at the third cycle and for the remainder of the study until PD or unacceptable toxicity, whichever occurs first.; Patients assigned to the chlorambucil arm will receive oral chlorambucil tablets at 0.8 mg/kg on Days 1 and 15 of each 28-day cycle for a total duration of 12 months (approximately 13 cycles).
Intervention MeSH terms: Lenalidomide; Chlorambucil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 450.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the safety and efficacy of lenalidomide as a first
      line therapy in treating patients with B-cell Chronic Lymphocytic Leukemia. This study will
      compare the effects (good and bad) of lenalidomide with chlorambucil.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Must sign an informed consent form.

          2. Age ≥ 65 years

          3. Must be able to adhere to the study visit schedule and other protocol requirements.

          4. Must have a documented diagnosis of B-cell CLL.

          5. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.

          6. Must agree to follow pregnancy precautions as required by the protocol.

          7. Must agree to receive counseling related to teratogenic and other risks of
             lenalidomide.

          8. Must agree not to donate blood or semen as defined by the protocol

        Exclusion Criteria:

          1. Prior treatment for B-cell CLL.

          2. Any medical condition, that would prevent the subject from signing the informed
             consent form.

          3. Active infections requiring systemic antibiotics.

          4. Systemic infection that has not resolved > 2 months prior to initiating lenalidomide

          5. Pregnant or lactating females.

          6. Participation in any clinical study or having taken any investigational therapy within
             28 days.

          7. Known presence of alcohol and/or drug abuse.

          8. Central nervous system (CNS) involvement.

          9. Prior history of malignancies, other than CLL, unless the subject has been free of the
             disease for ≥3 years. Exceptions include the following:

               -  Basal cell carcinoma of the skin

               -  Squamous cell carcinoma of the skin

               -  Carcinoma in situ of the cervix

               -  Carcinoma in situ of the breast

               -  Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

         10. History of renal failure requiring dialysis.

         11. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C
             Virus (HCV) infection.

         12. Prior therapy with lenalidomide.

         13. Evidence of TLS at screening

         14. Presence of specific hematology and/or chemistry abnormalities

         15. Uncontrolled hyperthyroidism or hypothyroidism

         16. Venous thromboembolism within one year

         17. ≥ Grade-2 neuropathy

         18. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia

         19. Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic
             leukemia]