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A Phase III Randomized Trial to Evaluate the Efficacy and Safety of Second-Line Therapy With Fludarabine Plus Alemtuzumab vs. Fludarabine Alone in Patients With B-Cell Chronic Lymphocytic Leukemia

Phase 3
18 Years
Not Enrolling
B-Cell Chronic Lymphocytic Leukemia

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Trial Information

A Phase III Randomized Trial to Evaluate the Efficacy and Safety of Second-Line Therapy With Fludarabine Plus Alemtuzumab vs. Fludarabine Alone in Patients With B-Cell Chronic Lymphocytic Leukemia

Inclusion Criteria:

- A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National
Cancer Institute Working Group (NCI WG) criteria.

- Relapsed or refractory disease after 1 prior regimen except patients who were
refractory to (i.e., progressed on) fludarabine or alemtuzumab therapy. Patients who
previously responded (complete response or partial response) to fludarabine or
alemtuzumab therapy, but who have relapsed at the time of study entry, may be
eligible but response to fludarabine or alemtuzumab therapy must have lasted >12
months (i.e., >12 months from a documented response to a documented relapse).

- Binet stage A, stage B, or stage C or Rai Stage I through IV disease with evidence of
progression as evidenced by the presence of one or more of the following:

I. Evidence of progressive marrow failure as manifested by: 1) a decrease in hemoglobin to
<11g/dL, or 2) a decrease in platelet count to <100 x 10^9/L within the previous 6 months,
or 3) a decrease in absolute neutrophil count (ANC) to <1.0 X 10^9/L.

II. Progressive splenomegaly to >2 cm below the left costal margin or other organomegaly.

III. Progressive lymphadenopathy.

IV. Progressive lymphocytosis with an increase of 50% over a 2-month period, or an
anticipated doubling time of less than 6 months.

- World Health Organization (WHO) performance status (PS) of 0 or 1.

- Life expectancy >12 weeks.

- Anti-cancer therapy, major surgery, or irradiation was completed >3 weeks before
randomization in this study. Patient must have recovered from the acute side effects
incurred as a result of previous therapy.

- Serum creatinine less than or equal to 2.0 x institutional upper limits of normal
(ULN) and calculated creatinine clearance (CrCl) greater than or equal to 30mL/min
using the Cockroft and Gault formula.

- Adequate liver function as indicated by a total bilirubin, AST, and ALT less than or
equal to 2 x the institutional ULN value, unless directly attributable to the
patient's tumor.

- Female patients with childbearing potential must have a negative serum pregnancy test
with 2 weeks of first dose of study drug(s). Male and female patients must agree to
use an effective contraceptive method while on study treatment, if appropriate, and
for a minimum of 6 months following study therapy.

- Signed, written informed consent.

Exclusion Criteria:

- Previously treated with >1 prior regimen for B-CLL.

- Previously treated with a fludarabine plus alemtuzumab (FluCAM) regimen for B-CLL.

- Positive Coombs test and actively hemolyzing.

- Absolute neutrophil count (ANC) <1.5 x 10^9/L or platelet count <75 x 10^9/L, unless
due to bone marrow involvement.

- Medical condition requiring chronic use of pharmacologic doses of oral
corticosteroids, i.e. anything other than replacement dose levels.

- History of anaphylaxis following exposure to monoclonal antibodies.

- Use of investigational agents within 6 weeks prior to study randomization.

- Active infection or history of severe infection (grade 4) within 3 months prior to
study randomization.

- Known to be human immunodeficiency virus (HIV) positive.

- Autoimmune thrombocytopenia.

- Active second malignancy.

- Known central nervous system (CNS) involvement with B-CLL.

- Other severe, concurrent diseases, including tuberculosis, mental disorders, serious
cardiac functional capacity (Class III or IV as defined by the New York Heart
Association Classification), severe diabetes, severe hypertension, pulmonary disease
(chronic obstructive pulmonary disease [COPD] with hypoxemia), or major organ
malfunction (liver, kidney) that could interfere with the patient's ability to
participate in the study.

- Pregnant or nursing women.

- Patients that have progressed with more aggressive B-cell cancers such as Richter's

- Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive
hepatitis B serologies without prior immunization.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment

Outcome Description:

Progression-free survival was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease (PD) as determined by the treatment-blinded IRRP, or death due to any cause. Results are expressed in months.

Outcome Time Frame:

Up to 6 years

Safety Issue:


Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

July 2004

Completion Date:

June 2010

Related Keywords:

  • B-cell Chronic Lymphocytic Leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



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