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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


Phase 2
18 Years
N/A
Not Enrolling
Both
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

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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.


Inclusion Criteria:



- Specific Diagnosis of B-Cell CLL

- An absolute lymphocytosis of > 5,000/μL

- Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes

- Bone marrow examination must include at least a unilateral aspirate and biopsy; the
aspirate smear must show > 30% of all nucleated cells to be lymphoid or the bone
marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement
by CLL; the overall cellularity must be normocellular or hypercellular

- Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal
population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the
absence of other pan-T-cell markers; additionally, the B-cells must be monoclonal
with regard to expression of either κ or λ and have surface immunoglobulin expression
of low density; patients with bright surface immunoglobulin levels must have CD23
co-expression

- Patients must be in the intermediate- or high-risk categories of the modified
three-stage Rai staging system (i.e., stages I, II, III, or IV)

- Patients in the intermediate-risk group must have evidence of active disease as
demonstrated by at least one of the following criteria:

- Massive or progressive splenomegaly, hepatomegaly and/or lymphadenopathy;

- Presence of weight loss > 10% over the preceding 6 month period;

- Grade 2 or 3 fatigue;

- Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of
infection;

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

- No prior therapy for CLL including corticosteroids for autoimmune complications that
have developed since the initial diagnosis of CLL

- No medical condition requiring chronic use of oral corticosteroids

- Performance Status 0 - 2

- Due to alterations in host immunity, patients with HIV may not be enrolled

- Due to the unknown teratogenic potential of alemtuzumab, pregnant or nursing women
may not be enrolled; women and men of reproductive potential should agree to use an
effective means of birth control

- Creatinine =< 1.5 x upper limit of institutional normal value

- Coomb's Testing NEGATIVE

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With a Complete Response After Treatment With Fludarabine & Rituximab Followed by Alemtuzumab

Outcome Description:

A complete response, as defined by the National Cancer Institute Working Group (NCIWG): - CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy

Outcome Time Frame:

Duration of treatment (up to 13.5 months)

Safety Issue:

No

Principal Investigator

Thomas Lin

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02812

NCT ID:

NCT00098670

Start Date:

October 2004

Completion Date:

Related Keywords:

  • 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

Name

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Cancer and Leukemia Group BChicago, Illinois  60606