Safety and Efficacy of SDX-101 (R-Etodolac) in Combination With Chlorambucil, and That of Chlorambucil Alone, in Patients With Chronic Lymphocytic Leukemia (CLL)

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Randomized, Multi-Center, Phase II Study to Investigate the Safety and Efficacy of SDX-101 (R-etodolac) in Combination With Chlorambucil, and That of Chlorambucil Alone, in Patients With Chronic Lymphocytic Leukemia (CLL)

Conditions
-----------------
Chronic Lymphocytic Leukemia

Intervention / Treatment
-----------------
* Drug: Chlorambucil
* Drug: R-etodolac + chlorambucil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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). 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. No prior chemotherapy for CLL. Age ≥ 18 at signing of informed consent. World Health Organization (WHO) performance status ≤ 0-2 (Appendix B). Platelet count > 50,000/μL, hemoglobin > 8.0 g/dl and absolute neutrophil count > 1000/μL. Renal function ≤ 1.5 x upper limit normal (blood urea nitrogen [BUN], serum creatinine) Liver function ≤ 1.5 times upper limit of normal (total bilirubin, SGOT (AST) and SGPT (ALT) values). 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. Signed EC/IRB-approved informed consent by patient prior to all study related procedures. Exclusion Criteria: Active autoimmune manifestation of CLL such as ongoing hemolytic anemia or ITP 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. Chronic viral infection: positive hepatitis B or hepatitis C serology, known positive for human immunodeficiency virus (HIV) or human T-leukemia/lymphoma virus (HTLV). Transformation to an aggressive B-cell malignancy such as Richter's transformation, prolymphocytic leukemia (PLL) or large B-cell lymphoma. Clinical evidence of CNS involvement with CLL. Serious infection, medical condition, or psychiatric condition that, in the opinion of the investigator, might interfere with the achievement of the study objectives. Treatment with any investigational agent within 4 weeks of study entry. The use of steroids, nonsteroidal anti-inflammatory drugs, regardless of indication (excluding prophylactic use of aspirin for prevention of acute myocardial infarction or stroke) Pregnancy or currently breast feeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chlorambucil<br>Regime A | Drug: Chlorambucil<br>* Chlorambucil 2mg tablets<br>* Other names: SDX-101;|
| Experimental: R-etodolac with chlorambucil<br>Regime B | Drug: R-etodolac + chlorambucil<br>* R-etodolac 600mg tablets + chlorambucil 2mg tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Marrow Biopsy or Aspiration | Overall response rate assessment according to National Cancer Institute-Working Group (NCI-WG) criteria using cytogenetic and biomarker evaluations. | Baseline + 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytogenetic and biomarker evaluations + adverse events | Cytogenetic and biomarker evaluations performed on day 14 (for regimen B) and day 1 (for regimen A) to assess Safety and Tolerability. Study visits to assess safety occur every 2 weeks for 3 months, then every month thereafter. Safety assessments include: medical history, physical examinations, vital sign measurements, adverse event assessment, routine hematology and serum chemistry tests, urinalysis, and ECGs. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Lymphocytic Leukemia, CLL, Leukemia