Clinical trial NCT01558167 (phase 1/phase 2, status: completed)
Conditions: chronic lymphocytic leukemia
ICD codes: C91.11, C91.12, C91.10
Drugs: bendamustine, rituximab, lenalidomide
SMILES: NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O
Eligibility criteria:

        Inclusion Criteria:

          1. Signed written informed consent.

          2. 18 years of age or older.

          3. Medically fit patients without relevant comorbidity, defined as total CIRS score ≤ 6.

          4. WHO performance status of 0-2.

          5. Confirmed diagnosis of CLL in need of treatment (Binet C or A/B with active disease)
             according to the updated IWCLL guidelines (Hallek et al. 2008).

          6. Life expectancy > 12 weeks.

          7. Relapsed or refractory disease after at least one, but no more than 3 prior regimens.
             Patients who previously received bendamustine (with or without rituximab) must have
             had at least a partial response with duration of response of at least six months.

          8. CLL therapy, major surgery, or irradiation for CLL was completed > 4 weeks before
             registration in this study. Patients must have recovered from the acute side effects
             incurred as a result of previous therapy.

          9. Patient is able and willing to receive adequate anticoagulation as specified in this
             protocol.

         10. Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 the
             institutional ULN value, unless directly attributable to the patient's tumor.

         11. Creatinine clearance >60ml/min calculated according to the modified formula of
             Cockcroft and Gault or directly measured after 24h-urine collection.

         12. ANC > 1500/µl and platelet count > 75.000/μl, unless decrease is due to bone marrow
             involvement of CLL

         13. Negative serological hepatitis B test, negative testing of hepatitis C RNA, negative
             HIV test within 6 weeks prior to registration.

         14. Females of childbearing potential (FOCP) must understand that the study medication has
             a teratogenic risk and must agree to use, and be able to comply with effective
             contraception without interruption, 4 weeks before starting study drug, throughout
             study drug therapy (including dose interruptions) and for 6 months after the end of
             study drug therapy, even if she has amenorrhea. This applies unless the subject
             commits to absolute and continued abstinence confirmed on a monthly basis.

        Exclusion Criteria:

          1. Previously treated with > 3 prior regimens for CLL.

          2. Known central nervous system (CNS) involvement of CLL.

          3. Patients who have progressed with more aggressive B-cell cancers such as Richter's
             syndrome or are diagnosed with B-PLL.

          4. History of anaphylaxis following exposure to any of the used study-drugs and/or
             thalidomide.

          5. Evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be
             enrolled upon correction of electrolyte abnormalities).

          6. Participation in another clinical trial and/or use of investigational agents or
             concurrent anti cancer treatment within the last 4 weeks of registration.

          7. Other severe, concurrent diseases, including tuberculosis, mental disorders, serious
             cardiac functional capacity (class III or IV as defined by the New York Heart
             Association Classification), severe diabetes, severe hypertension, pulmonary disease
             (COPD with hypoxemia), or major organ malfunction that could interfere with the
             patient's ability to participate in the study.

          8. Pregnant or lactating women.

          9. Any circumstance at the time of study entry that would preclude completion of the
             study or the required follow-up.

         10. Active secondary malignancy requiring treatment (except basal cell carcinoma or
             malignant tumor curatively treated by surgery) within the last 5 years before
             registration.

         11. Active bacterial, viral or fungal infection.

         12. Medical condition requiring prolonged use of oral corticosteroids (> 1 month).

         13. Cerebral dysfunction, legal incapacity.

         14. Patients with contraindications according to Summary of Product Characteristics or
             Investigator's Brochure.

         15. Patients who are employees of the Sponsor (University of Cologne) or the study sites.

         16. Persons placed in an institution by legal or official order.