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A Phase II Randomized Trial Comparing Standard and Low Dose Rituximab: Initial Treatment of Progressive Chronic Lymphocytic Leukemia in Elderly Patients Using Alemtuzumab, and Rituximab

Phase 2
65 Years
Open (Enrolling)

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Trial Information

A Phase II Randomized Trial Comparing Standard and Low Dose Rituximab: Initial Treatment of Progressive Chronic Lymphocytic Leukemia in Elderly Patients Using Alemtuzumab, and Rituximab



- To compare the rate of complete and overall response in elderly patients with
progressive chronic lymphocytic leukemia (CLL) treated with one of two doses of
rituximab combined with alemtuzumab to determine if the use of modified-dose rituximab
significantly affects outcome.


- To monitor and assess toxicity of these regimens.

- To determine the overall and progression-free survival, time to clinical response, time
to next treatment, and duration of response in patients treated with these regimens

- To assess the correlation between risk stratification prognostic markers (i.e., CD38,
ZAP-70, FISH, and IgVH mutation) and clinical outcome.

- To assess response to these regimens using both the NCI-WG 96 criteria and an expanded
definition of response for patients in complete remission, including
immunohistochemical examination of the bone marrow and sensitive flow cytometry (4-6
color) of blood for minimal residual disease and CT scans for residual adenopathy.

- To determine the mechanism of action of rituximab and alemtuzumab and to determine
mechanisms of resistance of a subpopulation of CLL cells to these drugs.

OUTLINE: This is a multicenter study. Patients are stratified according to FISH risk (low
[13q14-] vs intermediate [12+, no abnormality, all other abnormalities] vs high
[17p13-,11q22-]). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15,
17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab IV on days 8, 15, 22, and 29
in course 1. In courses 2 and 3, patients receive alemtuzumab SC on days 1, 3, 5, 8,
10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17,
and 24. Treatment repeats every 28 days for up to 3 courses in the absence of disease
progression or unacceptable toxicity.

- Arm II: Patients receive alemtuzumab as in arm I. Patients also receive low-dose
rituximab IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in course 1 and
on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in courses 2 and 3. Treatment
repeats every 28 days for up to 3 courses in the absence of disease progression or
unacceptable toxicity.

Blood and bone marrow samples are collected periodically for cytogenetic and biomarker

After completion of study therapy, patients are followed up periodically for 5 years.

Inclusion Criteria


- Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:

- Minimum threshold peripheral lymphocyte count of 5 x 10^9/L (CLL variant) OR
palpable adenopathy > 1 cm or palpable splenomegaly (SLL variant)

- Immunophenotypic demonstrations of a population of B-lymphocytes (as defined by
CD19+) that are monoclonal (by light-chain exclusion) AND have ≥ 3 of the
following characteristics:

- CD5+

- CD23+

- Dim surface light chain expression

- Dim surface CD20 expression

- FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for
cyclin D1 expression (to exclude mantle cell lymphoma)

- Has progressive, symptomatic CLL, defined by at least one of the following:

- Weight loss > 10% within the past 6 months attributable to progressive CLL
(grade 2 or higher)

- Extreme fatigue attributable to progressive CLL (grade 3 or higher)

- Fevers > 100.5° F for 2 weeks without evidence of infection (grade 1 or higher)

- Night sweats without evidence of infection (drenching)

- Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or
platelet count < 100 x 10^9/L

- Rapidly progressive lymphadenopathy for which the largest node is ≤ 5 cm in any

- Largest lymph nodes involved in the neck, axilla, and groin need to be
measured and followed for response

- No massive splenomegaly > 6 cm below left costal margin, at rest, on clinical

- No lymphadenopathy > 5 cm in any diameter


- ECOG performance status 0-3

- Creatinine ≤ 2 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 times ULN

- AST ≤ 3.0 times ULN (unless due to CLL involvement of the liver)

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 12 months after
completion of study therapy

- None of the following comorbid conditions:

- New York Heart Association class III or IV heart disease

- Recent myocardial infarction (within the past month)

- Uncontrolled infection


- Serological evidence of active hepatitis B infection (HBsAg or HBeAg positive)

- Positive hepatitis C serology

- No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood
cell aplasia

- No other active primary malignancy requiring treatment or that limits survival to ≤ 2
years, except for in situ carcinoma of the cervix or breast or non-metastatic basal
cell or squamous cell carcinoma of the skin


- No prior treatment for CLL

- More than 4 weeks since prior major surgery

- No concurrent continuous systemic corticosteroids

- Prior corticosteroids are allowed but not at time of pre-registration to the

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Rate of complete and overall response

Safety Issue:


Principal Investigator

Clive S. Zent, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic



Study ID:




Start Date:

October 2010

Completion Date:

Related Keywords:

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



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