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 Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Chlorambucil Regime A |
Drug: Chlorambucil
Chlorambucil 2mg tablets
Other Names:
|
| Experimental: R-etodolac with chlorambucil Regime B |
Drug: R-etodolac + chlorambucil
R-etodolac 600mg tablets + chlorambucil 2mg tablets
|
Outcome Measures
Primary Outcome Measures
- Bone Marrow Biopsy or Aspiration [Baseline + 6 months]
Overall response rate assessment according to National Cancer Institute-Working Group (NCI-WG) criteria using cytogenetic and biomarker evaluations.
Secondary Outcome Measures
- Cytogenetic and biomarker evaluations + adverse events [6 months]
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.
Eligibility Criteria
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:
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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.).
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Evidence of progressive marrow failure as manifested by:
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A decrease in hemoglobin to < 10g/dL, or
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A decrease in platelet count to < 100 x 10(9)/L within the previous 6 months, or
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A decrease in absolute neutrophil count (ANC) to < 1.0 x 10(9)/L within 6 months
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Progressive lymphocytosis with an increase of > 50% over a 2 month period, or an anticipated doubling time of < 6 months.
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Massive nodes or clusters(i.e., > 10 cm in longest diameter) or progressive lymphadenopathy.
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Progressive splenomegaly to > 2cm below the left costal margin or other organomegaly with progressive increase over 2 consecutive clinical visits ≥ 2 weeks apart.
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No prior chemotherapy for CLL.
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Age ≥ 18 at signing of informed consent.
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World Health Organization (WHO) performance status ≤ 0-2 (Appendix B).
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Platelet count > 50,000/μL, hemoglobin > 8.0 g/dl and absolute neutrophil count > 1000/μL.
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Renal function ≤ 1.5 x upper limit normal (blood urea nitrogen [BUN], serum creatinine)
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Liver function ≤ 1.5 times upper limit of normal (total bilirubin, SGOT (AST) and SGPT (ALT) values).
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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.
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Signed EC/IRB-approved informed consent by patient prior to all study related procedures.
Exclusion Criteria:
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Active autoimmune manifestation of CLL such as ongoing hemolytic anemia or ITP
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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.
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Chronic viral infection: positive hepatitis B or hepatitis C serology, known positive for human immunodeficiency virus (HIV) or human T-leukemia/lymphoma virus (HTLV).
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Transformation to an aggressive B-cell malignancy such as Richter's transformation, prolymphocytic leukemia (PLL) or large B-cell lymphoma.
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Clinical evidence of CNS involvement with CLL.
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Serious infection, medical condition, or psychiatric condition that, in the opinion of the investigator, might interfere with the achievement of the study objectives.
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Treatment with any investigational agent within 4 weeks of study entry.
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The use of steroids, nonsteroidal anti-inflammatory drugs, regardless of indication (excluding prophylactic use of aspirin for prevention of acute myocardial infarction or stroke)
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Pregnancy or currently breast feeding.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chef du Service d'Hematologie Clinique CHU Clemenceau | Caen | France | ||
| 2 | Service maladies du sang CHRU- rue Michel Polonovski | Lille | France | ||
| 3 | Charité - Benjamin Franklin Medizinische Klinik III Hämatologie, Onkologie und Transfusionsmedizin | Berlin | Germany | ||
| 4 | Internistische Schwerpunktpraxis | Erlangen | Germany | ||
| 5 | Medizinische Poliklinik der Universität Hämatologie/Onkologie | Würzburg | Germany | ||
| 6 | Samodzielny Publiczny Szpital Kliniczny AM Klinika Hematologii | Bialystok | Poland | ||
| 7 | Samodzielny Publiczny Szpital Kliniczny Nr 1 Akademickie Centrum Kliniczne Akdemii Medycznej w Gdansku Klinika Hematologii | Gdansk | Poland | ||
| 8 | Uniwersytet Jagiellonski Collegium Medicum Katedra i Klinika Hematologii | Krakow | Poland | ||
| 9 | Wojewodzki Szpital Specjalistyczny im. M. Kopernika, Klinika Hematologii Instytutu Medycyny Wewnetrznej Uniwersytetu Medycznego w Lodzi | Lodz | Poland | ||
| 10 | Prywatna Praktyka Lekarska z Osrodkiem Badan Klinicznych Prof. L. Szczepanskiego | Lublin | Poland | ||
| 11 | Samodzielny Publiczny Centralny Szpital Kliniczny Katedra i Klinika Hematologii Onkologii i Chorob Wewnetrznych AM | Warszawa | Poland | ||
| 12 | Samodzielny Publiczny Szpital Kliniczny Nr 1 Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku | Wroclaw | Poland | ||
| 13 | Centrum för Hematologi Karolinska Universitetssjukhuset, Solna | Stockholm | Sweden | ||
| 14 | Hematologkliniken Karolinska Universitetssjukhuset, Huddinge | Stockholm | Sweden | ||
| 15 | Hematologkliniken Norrlands Universitetssjukhus | Umeå | Sweden | ||
| 16 | Hematologisektionen Medicincentrum Akademiska sjukhuset | Uppsala | Sweden | ||
| 17 | Royal Bournemouth Hospital Dept. of Haematology | Bournemouth | United Kingdom | ||
| 18 | Cardiff and Vale NHS Trust University Hospital of Wales | Cardiff | United Kingdom | ||
| 19 | Stobhill Hospital Department of Haematology | Glasgow | United Kingdom | ||
| 20 | Leeds General Infirmary Department of Haematology | Leeds | United Kingdom | ||
| 21 | Leicester Royal Infirmary Department of Oncology & Haematology | Leicester | United Kingdom | ||
| 22 | Nottingham City Hospital NHS Trust | Nottingham | United Kingdom |
Sponsors and Collaborators
- Cephalon
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SDX-101-03