Nonmyeloablative Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Lenalidomide; Fludarabine; Rituximab; Thymoglobulin; Stem Cell Transplantation; Bendamustine; Allopurinol
Intervention description: Starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months; 30 mg/m^2 intravenously daily on days -5, -4, -3.; 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8.; 1.0 mg/kg intravenously over 4 hours (day -2 and -1).; On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes.; 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine).; 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.
Intervention MeSH terms: Rituximab; Fludarabine; Fludarabine phosphate; Lenalidomide; Bendamustine Hydrochloride; Allopurinol; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Nonmyeloablative Stem Cell Transplantation; Chronic Lymphocytic Leukemia; CLL; Immunomanipulation; Fludarabine; Lenalidomide; Rituximab; Thymoglobulin; Stem Cell Transplantation

Summary:

      The goal of this clinical research study is to learn if lenalidomide, when given with a stem
      cell transplant and chemotherapy (bendamustine, fludarabine, and rituximab), can help to
      control CLL. The safety of this treatment combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18-75 years at the time of signing the informed consent form.

          2. Disease: CLL in relapse, after failing conventional chemo-antibody combination
             therapy; CLL patients who failed to achieve CR with frontline conventional
             chemo-antibody; CLL patients with 17p deletion; CLL in Richter's.

          3. Able to adhere to the study visit schedule and other protocol requirements.

          4. Donor: HLA compatible related (HLA-A,-B,-DRBI matched or with one-antigen mismatched)
             or HLA compatible unrelated.

          5. ECOG performance status of </= 2 at study entry

          6. FEV1, FVC and DLCO >/= 40%.

          7. Left ventricular EF > 40% with no uncontrolled arrhythmias or symptomatic heart
             disease.

          8. Serum creatinine </= 1.6 mg/dL. Serum bilirubin < 1.6 mg/dL.

          9. SGPT < 2x upper limit of normal.

         10. Voluntary signed, written IRB-approved informed consent before performance of any
             study-related procedure not part of normal medical care, with the understanding that
             consent may be withdrawn by the subject at any time without prejudice to future
             medical care.

         11. All previous cancer therapy, including radiation, hormonal therapy and surgery, must
             have been discontinued at least 3 weeks prior to treatment in this study.

         12. 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.

         13. 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 prior to
             study entry.

         14. Disease must be chemosensitive (ie, patients must have PR or better based on CT Scans,
             PET Scan, and bone marrow biopsy).

         15. Patients suspected to have Richter's transformation (such as elevated LDH) and/or who
             are PET positive, should have a lymph node biopsy to assess histological status of the
             disease

         16. Patients must be off of alemtuzumab for 6 weeks prior to consenting.

        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 the study.

          4. Use of any other experimental drug or therapy within 28 days of baseline.

          5. Known hypersensitivity to thalidomide, lenalidomide, bendamustine, fludarabine. For
             patients will unrelated donors: Known hypersensitivity to thymoglobulin.

          6. The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs.

          7. Concurrent use of other anti-cancer agents or treatments.

          8. Known positive for HIV or infectious hepatitis, type A, B or C.

          9. Sinuses should be evaluated by either CT neck or CT sinuses to exclude infections

         10. Deep-vein thrombosis or pulmonary embolism within 3 months of study entry.

         11. History of serious infection requiring hospitalization within the last 3 months of
             consenting.