Safety and Efficacy of SDX-101 (R-Etodolac) in Combination With Chlorambucil, and That of Chlorambucil Alone, in Patients With Chronic Lymphocytic Leukemia (CLL)
Safety and Efficacy of SDX-101 (R-Etodolac) in Combination With Chlorambucil, and That of Chlorambucil Alone, in Patients With Chronic Lymphocytic Leukemia (CLL)
This is a Phase 2, multi-center, open label, randomized clinical study to evaluate the safety
 and efficiency of SDX-101 in combination with chlorambucil (CLB) and chlorambucil alone in
 Chronic Lymphocytic Leukaemia (CLL) patients. The study treatment period will be
 approximately 24-26 weeks with a follow-up period of approximately 8 weeks. Following the end
 of treatment, patients with a confirmed complete response, partial response or stable disease
 will be followed for up to 2 years to assess time to disease progression. Approximately 80
 patients with documented diagnosis of B-cell CLL by standard clinical and immunophenotyping
 criteria will be enrolled into the SDX-101-03 study. This study is being conducted in the
 following European countries: France, Germany, Poland, Sweden and the United Kingdom.
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.