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

Chronic Lymphocytic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00151736
• Other study ID #: SDX-101-03
• Status: Terminated
• Phase: Phase 2
• First received: September 7, 2005
• Last updated: June 8, 2012
• Start date: September 2004
• Est. completion date: February 2008

Study information

• Verified date: June 2012
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 88
• Est. completion date: February 2008
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Chlorambucil
Chlorambucil 2mg tablets
• R-etodolac + chlorambucil
R-etodolac 600mg tablets + chlorambucil 2mg tablets

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cephalon

Countries where clinical trial is conducted

France,  Germany,  Poland,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes