Clinical trial NCT00151736: Safety and Efficacy of SDX-101 (R-Etodolac) in Combination With Chlorambucil, and That of Chlorambucil Alone, in Patients With Chronic Lymphocytic Leukemia (CLL)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
CLL
Leukemia
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2005-09-09
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Bone Marrow Biopsy or Aspiration
timeFrame: Baseline + 6 months
Secondary outcomes:
measure: Cytogenetic and biomarker evaluations + adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Caen
country: France
facility: Chef du Service d'Hematologie Clinique CHU Clemenceau
city: Lille
country: France
facility: Service maladies du sang CHRU- rue Michel Polonovski
city: Berlin
country: Germany
facility: Charité - Benjamin Franklin Medizinische Klinik III Hämatologie, Onkologie und Transfusionsmedizin
city: Erlangen
country: Germany
facility: Internistische Schwerpunktpraxis
city: Würzburg
country: Germany
facility: Medizinische Poliklinik der Universität Hämatologie/Onkologie
city: Bialystok
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny AM Klinika Hematologii
city: Gdansk
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 Akademickie Centrum Kliniczne Akdemii Medycznej w Gdansku Klinika Hematologii
city: Krakow
country: Poland
facility: Uniwersytet Jagiellonski Collegium Medicum Katedra i Klinika Hematologii
city: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. M. Kopernika, Klinika Hematologii Instytutu Medycyny Wewnetrznej Uniwersytetu Medycznego w Lodzi
city: Lublin
country: Poland
facility: Prywatna Praktyka Lekarska z Osrodkiem Badan Klinicznych Prof. L. Szczepanskiego
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny Katedra i Klinika Hematologii Onkologii i Chorob Wewnetrznych AM
city: Wroclaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
city: Stockholm
country: Sweden
facility: Centrum för Hematologi Karolinska Universitetssjukhuset, Solna
city: Stockholm
country: Sweden
facility: Hematologkliniken Karolinska Universitetssjukhuset, Huddinge
city: Umeå
country: Sweden
facility: Hematologkliniken Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Hematologisektionen Medicincentrum Akademiska sjukhuset
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital Dept. of Haematology
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale NHS Trust University Hospital of Wales
city: Glasgow
country: United Kingdom
facility: Stobhill Hospital Department of Haematology
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary Department of Haematology
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary Department of Oncology & Haematology
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
Study officials:
References: