Skip to main content
OpenTrials
Completed

NCT Number: NCT00281918

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Leukemia Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Gosford Hospital, Gosford, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Rituximab

Drug

Intravenous repeating dose

Cyclophosphamide

Drug

Intravenous repeating dose

fludarabine phosphate

Drug

Intravenous repeating dose

Primary outcomes

  1. Progression-free Survival (PFS)

    Time frame: Median observation time at time of analysis was approximately 21 months

    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.

  2. Final Analysis: Time to Progression-free Survival Event

    Time frame: Median observation time was approximately 66.4 months

    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.

Secondary outcomes

  1. Event-free Survival (EFS)

    Time frame: Median observation time at time of analysis was approximately 21 months

    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.

  2. Overall Survival (OS)

    Time frame: Median observation time at time of analysis was approximately 21 months

    Overall survival (OS) was defined as the time between randomization and the date of death due to any cause. Median OS was not reached.

  3. Disease-free Survival (DFS) of Patients With Confirmed Complete Response (CR).

    Time frame: Median observation time at time of analysis was approximately 21 months

    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.

  4. Final Analysis: Time to Overall Survival Event

    Time frame: Median observation time was approximately 66.4 months

    Overall survival (OS) was defined as the time between randomization and the date of death due to any cause.

  5. Final Analysis: Time to Event-free Survival Event

    Time frame: Median observation time was approximately 66.4 months

    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.

  6. 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

    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

  7. Final Analysis: Duration of Response

    Time frame: Median observation time was approximately 66.4 months

    Duration of response was defined as the time from the first documented Complete Response, Partial Response to disease progression or death by any cause.

  8. Final Analysis: Percentage of Participants With Complete Response (CR) and Partial Response

    Time frame: Median observation time was approximately 66.4 months

    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.

  9. Final Analysis: Time to New Treatment for Chronic Lymphocytic Leukemia(CLL)

    Time frame: Median observation time was approximately 66.4 months

    The time from randomization to the start of a new treatment.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Collaborators

  • German CLL Study Group

Registry information

Official study 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

Acronym: CLL-8

Important dates

Study start
2003
Primary completion
2007
Study completion
2011
First posted
Jan 25, 2006
Registry last updated
Sep 19, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.