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

This study has been completed.
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: September 9, 2013
Last verified: September 2013

January 24, 2006
September 9, 2013
July 2003
July 2007   (final data collection date for primary outcome measure)
  • 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.
  • Final Analysis: Time to Progression-free Survival Event [ Time Frame: Median observation time was approximately 66.4 months ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time between randomization and the date of first documented disease progression, relapse or death by any cause, whichever came first.
Not Provided
Complete list of historical versions of study NCT00281918 on ClinicalTrials.gov Archive Site
  • 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 to relapse or death. Median DFS was not reached.
  • Final Analysis: Time to Overall Survival Event [ Time Frame: Median observation time was approximately 66.4 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.
  • Final Analysis: Time to Event-free Survival Event [ Time Frame: Median observation time was approximately 66.4 months ] [ Designated as safety issue: No ]
    Event-free survival was defined as the time between randomization and the date of disease progression, relapse, start of new Chronic Lymphocytic Leukemia treatment or death by any cause.
  • Final Analysis: Time to Disease-free Survival (DFS) Event in Participants With Complete Response (CR) [ Time Frame: Median observation time was approximately 66.4 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 to relapse or death
  • Final Analysis: Duration of Response [ Time Frame: Median observation time was approximately 66.4 months ] [ Designated as safety issue: No ]
    Duration of response was defined as the time from the first documented Complete Response, Partial Response to disease progression or death by any cause.
  • Final Analysis: Percentage of Participants With Complete Response (CR) and Partial Response [ Time Frame: Median observation time was approximately 66.4 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. Partial response is defined as a decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment.
  • Final Analysis: Time to New Treatment for Chronic Lymphocytic Leukemia(CLL) [ Time Frame: Median observation time was approximately 66.4 months ] [ Designated as safety issue: No ]
    The time from randomization to the start of a new treatment.
Not Provided
Not Provided
Not Provided
 
Fludarabine and Cyclophosphamide With or Without Rituximab in Patients With Previously Untreated Chronic B-Cell Lymphocytic Leukemia
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Drug: Rituximab
    Intravenous repeating dose
  • Drug: Cyclophosphamide
    Intravenous repeating dose
  • Drug: Fludarabine Phosphate
    Intravenous repeating dose
  • Experimental: Fludarabine+Cyclophosphamide+Rituximab (FCR)
    Interventions:
    • Drug: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Fludarabine Phosphate
  • Active Comparator: Fludarabine+Cyclophosphamide (FC)
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Fludarabine Phosphate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
817
October 2011
July 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   Belgium,   Czech Republic,   Denmark,   France,   Germany,   Israel,   Italy,   New Zealand,   Spain
 
NCT00281918
CDR0000454560, GCLLSG-CLL-8, EU-20560, ML17102
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
German CLL Study Group
Study Chair: Michael Hallek, MD Medizinische Universitaetsklinik I at the University of Cologne
Hoffmann-La Roche
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP