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

Roche

Status and phase: Completed; Phase 3

Conditions: Leukemia

Treatments: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Drug: Rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00281918

CDR0000454560

ML17102

EU-20560

GCLLSG-CLL-8

Details and patient eligibility

About

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.

Enrollment: 817 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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817 participants in 2 patient groups

Fludarabine+Cyclophosphamide+Rituximab (FCR)

Experimental group

Treatment:

Drug: Rituximab

Drug: Fludarabine Phosphate

Drug: Cyclophosphamide

Fludarabine+Cyclophosphamide (FC)

Active Comparator group

Treatment:

Drug: Fludarabine Phosphate

Drug: Cyclophosphamide