Trial Information

A Phase II Study of Fludarabine + Rituximab Induction Followed by Alemtuzumab (Campath-1H, NSC #715969, IND #10864) Administered Subcutaneously as Consolidation in Untreated Patients With B-Cell Chronic Lymphocytic Leukemia

PRIMARY OBJECTIVES:

I. To determine the rate of complete response and toxicity of concurrent treatment with
fludarabine and rituximab followed by consolidative alemtuzumab in patients with previously
untreated, but symptomatic, CLL.

II. To determine if alemtuzumab improves the CR rate with acceptable toxicity when
administered as consolidation therapy following induction therapy with fludarabine and
rituximab.

III. To estimate the progression-free and overall survival of high risk (VH gene unmutated
and those with p53 dysfunction) and low-risk (others) patients following therapy with
fludarabine and rituximab induction and consolidative alemtuzumab.

IV. To determine the frequency of molecular (PCR) remission following fludarabine and
rituximab induction therapy and alemtuzumab consolidation therapy and if this serves as a
surrogate marker for prolonged progression-free and overall survival.

SECONDARY OBJECTIVES:

I. To determine the effect of concurrent treatment with fludarabine and rituximab followed
by consolidative alemtuzumab on recovery of T-cells, NK cells, and serum immunoglobulin
levels.

II. To determine clinical and molecular features that predict for poor response to
fludarabine and rituximab induction and subsequent alemtuzumab consolidation therapy.

III. To assess preliminarily the molecular features of CLL at relapse in patients responding
to chemoimmunotherapy for CLL.

IV. To determine the frequency of patients who remain at high risk for progression of CLL
despite this therapy and who are thus eligible for nonmyeloablative stem cell
transplantation studies such as CALGB 109901.

V. To perform limited rituximab pharmacokinetics to determine the ideal schedule of
administration for a subsequent rituximab maintenance treatment approach following induction
therapy with fludarabine and rituximab.

OUTLINE:

Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5
of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days
1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease
progression.

Approximately 4 months after completion of induction therapy, patients achieving a partial
response, nodular partial response, or stable disease receive consolidation therapy
comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6
courses in the absence of disease progression.

Patients are followed at 2 months, every 3 months for 1 year, and then every 6 months for 7
years from study entry.