Clinical trial NCT00151736 (phase 2, status: terminated)
Conditions: chronic lymphocytic leukemia
ICD codes: C91.11, C91.12, C91.10
Drugs: chlorambucil, r-etodolac + chlorambucil
SMILES: OC(=O)CCCC1=CC=C(C=C1)N(CCCl)CCCl, OC(=O)CCCC1=CC=C(C=C1)N(CCCl)CCCl
Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of B-cell CLL by standard clinical and immunophenotypic criteria as
             specified by the NCI working group revised guidelines for diagnosis and treatment of
             CLL(32).

          2. Binet stages A-C with evidence of active disease requiring treatment by the presence
             of one or more of the following at the time of study entry:

               -  Disease related B symptoms (Fever > 38C [100.5F] for ≥ 2 weeks without evidence
                  of infection, night sweats without evidence of infection, weight loss > 10%
                  within previous 6 mo.).

               -  Evidence of progressive marrow failure as manifested by:

               -  A decrease in hemoglobin to < 10g/dL, or

               -  A decrease in platelet count to < 100 x 10(9)/L within the previous 6 months, or

               -  A decrease in absolute neutrophil count (ANC) to < 1.0 x 10(9)/L within 6 months

               -  Progressive lymphocytosis with an increase of > 50% over a 2 month period, or an
                  anticipated doubling time of < 6 months.

               -  Massive nodes or clusters(i.e., > 10 cm in longest diameter) or progressive
                  lymphadenopathy.

               -  Progressive splenomegaly to > 2cm below the left costal margin or other
                  organomegaly with progressive increase over 2 consecutive clinical visits ≥ 2
                  weeks apart.

          3. No prior chemotherapy for CLL.

          4. Age ≥ 18 at signing of informed consent.

          5. World Health Organization (WHO) performance status ≤ 0-2 (Appendix B).

          6. Platelet count > 50,000/μL, hemoglobin > 8.0 g/dl and absolute neutrophil count >
             1000/μL.

          7. Renal function ≤ 1.5 x upper limit normal (blood urea nitrogen [BUN], serum
             creatinine)

          8. Liver function ≤ 1.5 times upper limit of normal (total bilirubin, SGOT (AST) and SGPT
             (ALT) values).

          9. Female patients of childbearing potential must have a negative pregnancy test (serum
             or urine Beta-human chorionic gonadotropin, Beta-HCG); men and women of reproductive
             potential must employ effective contraceptive methods while on study therapy, and for
             2 months following completion of treatment.

         10. Signed EC/IRB-approved informed consent by patient prior to all study related
             procedures.

        Exclusion Criteria:

          1. Active autoimmune manifestation of CLL such as ongoing hemolytic anemia or ITP

          2. History of a second malignancy with the exception of cervical cancer,or resected basal
             cell carcinoma or other malignancies with no evidence of recurrence 5 or more years
             since diagnosis.

          3. Chronic viral infection: positive hepatitis B or hepatitis C serology, known positive
             for human immunodeficiency virus (HIV) or human T-leukemia/lymphoma virus (HTLV).

          4. Transformation to an aggressive B-cell malignancy such as Richter's transformation,
             prolymphocytic leukemia (PLL) or large B-cell lymphoma.

          5. Clinical evidence of CNS involvement with CLL.

          6. Serious infection, medical condition, or psychiatric condition that, in the opinion of
             the investigator, might interfere with the achievement of the study objectives.

          7. Treatment with any investigational agent within 4 weeks of study entry.

          8. The use of steroids, nonsteroidal anti-inflammatory drugs, regardless of indication
             (excluding prophylactic use of aspirin for prevention of acute myocardial infarction
             or stroke)

          9. Pregnancy or currently breast feeding.