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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Chlorambucil; Drug: R-etodolac + chlorambucil

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chlorambucil; Regime A	Drug: Chlorambucil; Chlorambucil 2mg tablets; Other Names: SDX-101
Experimental: R-etodolac with chlorambucil; Regime B	Drug: R-etodolac + chlorambucil; R-etodolac 600mg tablets + chlorambucil 2mg tablets

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

Collaborators and Investigators

• Sponsor: Cephalon

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): February 1, 2006
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 9, 2005

Study Record Updates

• Last Update Posted (Estimate): June 11, 2012
• Last Update Submitted That Met QC Criteria: June 8, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Leukemia; CLL; Chronic Lymphocytic Leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Cyclooxygenase 2 Inhibitors; Etodolac; Chlorambucil
• Other Study ID Numbers: SDX-101-03