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Fludarabine and Cyclophosphamide With or Without Rituximab in Patients With Previously Untreated Chronic B-Cell Lymphocytic Leukemia (CLL-8)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
German CLL Study Group
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00281918
First received: January 24, 2006
Last updated: November 20, 2012
Last verified: November 2012
History of Changes
  Purpose

This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared to fludarabine and cyclophosphamide in treating patients with B-cell chronic lymphocytic leukemia.


Condition Intervention Phase
Leukemia
 Drug: Rituximab
Drug: Cyclophosphamide
Drug: Fludarabine Phosphate
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Trial of Combined Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) Versus Chemotherapy With Fludarabine and Cyclophosphamide (FC) Alone in Patients With Previously Untreated Chronic Lymphocytic Leukaemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Median observation time at time of analysis was approximately 21 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) was defined as the time between randomization and the date of first documented disease progression, relapse or death by any cause, whichever came first.


Secondary Outcome Measures:
  • Event-free Survival (EFS) [ Time Frame: Median observation time at time of analysis was approximately 21 months ] [ Designated as safety issue: No ]
    Event-free survival (EFS) was defined as the time between randomization and the date of disease progression, relapse, start of new CLL treatment or death by any cause.

  • Overall Survival (OS) [ Time Frame: Median observation time at time of analysis was approximately 21 months ] [ Designated as safety issue: No ]
    Overall survival (OS) was defined as the time between randomization and the date of death due to any cause. Median OS was not reached.

  • Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR). [ Time Frame: Median observation time at time of analysis was approximately 21 months ] [ Designated as safety issue: No ]
    CR is defined by at least 8 weeks of: 1)Absence of lymphadenopathy 2)No hepatomegaly or splenomegaly 3)Absence of B-symptoms 4)Normal blood count 5)Bone marrow aspirate and biopsy 8 weeks after the clinical and laboratory results demonstrated that a CR was achieved. A marrow sample had to be normocellular for age with less than 30% lymphocytes. Lymphoid nodules had to be absent. If marrow was hypocellular,a repeat biopsy was taken 4 weeks later and samples were re-reviewed in conjunction with the prior pathology. DFS was calculated from time of CR relapse or death. Median DFS was not reached.


Enrollment: 817
Study Start Date: July 2003
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine+Cyclophosphamide+Rituximab (FCR) Drug: Rituximab
Intravenous repeating dose
Drug: Cyclophosphamide
Intravenous repeating dose
Drug: Fludarabine Phosphate
Intravenous repeating dose
Active Comparator: Fludarabine+Cyclophosphamide (FC) Drug: Cyclophosphamide
Intravenous repeating dose
Drug: Fludarabine Phosphate
Intravenous repeating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosed B-cell chronic lymphocytic leukemia (CLL) defined by the National Cancer Institute (NCI) Working Group criteria

  • Meets 1 of the following criteria:

    • Binet stage C disease

    • Binet stage B disease AND ≥ 1 of the following signs or symptoms*:

      • B symptoms (night sweats, weight loss ≥ 10% within the previous 6 months, fevers > 38°C or 100.4°F for ≥ 2 weeks without evidence of infection), or constitutional symptoms (fatigue)
      • Continuous progression (doubling of peripheral lymphocyte count within the past 6 months and absolute lymphocyte count > 50 G/I)
      • Evidence of progressive marrow failure as manifested by the development/worsening of anemia and/or thrombocytopenia
      • Massive, progressive or painful splenomegaly or hypersplenism
      • Massive lymph nodes or lymph node clusters (> 10 cm in longest diameter), danger of organ complications through large lymphoma (e.g., vascular compression or tracheal narrowing), or progressive lymphadenopathy
      • Occurrence of symptomatic hyperviscosity problems at leukocyte counts > 200 G/I (symptomatic leukostasis) NOTE: * Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for eligibility
  • No Binet stage A disease
  • No transformation to an aggressive B-cell malignancy (e.g., diffuse large cell lymphoma, Richter's syndrome, or prolymphocytic leukemia)

PATIENT CHARACTERISTICS:

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Cumulative Illness Rating Scale (CIRS) score > 6
  • Life expectancy > 6 months
  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • Alkaline phosphatase and transaminases ≤ 2 times ULN
  • Creatinine clearance ≥ 70 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study treatment
  • No known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs
  • No cerebral dysfunction that precludes chemotherapy
  • No active bacterial, viral, or fungal infection
  • No clinically significant autoimmune cytopenia or Coombs-positive hemolytic anemia
  • No other active malignancy requiring concurrent treatment except basal cell carcinoma or tumors treated curatively by surgery
  • No medical or psychological condition that would preclude study therapy
  • No concurrent disease that requires prolonged (> 1 month) therapy involving glucocorticoids

PRIOR CONCURRENT THERAPY:

  • No previous treatment of CLL by chemotherapy, radiotherapy, or immunotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00281918

  Show 162 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
German CLL Study Group
Investigators
Study Chair: Michael Hallek, MD Medizinische Universitaetsklinik I at the University of Cologne
  More Information

Additional Information:
Clinical Study Report Synopsis  This link exits the ClinicalTrials.gov site

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00281918     History of Changes
Other Study ID Numbers: CDR0000454560, GCLLSG-CLL-8, EU-20560, ML17102
Study First Received: January 24, 2006
Results First Received: December 21, 2009
Last Updated: November 20, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Hoffmann-La Roche:
B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Rituximab
Fludarabine
Vidarabine
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 22, 2013