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Weekly Subcutaneous Alemtuzumab and Rituximab for Relapsed CLL

Phase 1/Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia

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Trial Information

Weekly Subcutaneous Alemtuzumab and Rituximab for Relapsed CLL

This study proposes to combine alemtuzumab, which effectively treats peripheral blood and
bone marrow disease in CLL, with rituximab, which has activity in lymph node disease, in a
streamlined and convenient administration schedule. Preclinical data support synergistic
interaction of the two. The primary objectives are (1) to determine the overall and
complete response (CR) rate in patients with relapsed CLL and to determine the safety of the
combination, and (2) the safety of higher doses of alemtuzumab at less frequent intervals.
Secondary objectives are (1) to describe the duration of response, progression-free
survival, and overall survival in patients not proceeding to allo transplant, (2) to
determine the improvement in overall and complete response associated with administration of
a 2nd eight week course of therapy, and (3) to assess minimal residual disease in certain
patients and to correlate those results with survival. If at least 16 responses are
observed among 35 patients, then the treatment will be considered promising.

The development of antibody therapies has held promise for CLL, since CLL therapies have
been palliative, with no established therapy shown to improve survival. Studies have
suggested that in contrast to what is seen with fludarabine and alkylating agents, response
rates to alemtuzumab are maintained in CLL subjects with P53 mutations. Tolerability of
rituximab and its major activity in nodes make it an attractive candidate for combination
with alemtuzumab.

This is a single center (DF/HCC), single arm, multi cohort, phase I study, with treatment on
an outpatient basis. If the initial alemtuzumab dose of 30 mg sc d1, 3,and 5 is tolerated,
there will be dose escalations in cohorts of 3, up to 90 mg d1 per week. Following
determination of a maximum tolerated dose, accrual of all remaining patients will occur at
that dose. Subjects will be restaged after 8 weeks of therapy, and may proceed to
transplant. If deriving benefit, but not in CR, subjects may receive another 8 weeks of

Inclusion Criteria:

- Subjects must be diagnosed with B-CLL / SLL (B-chronic lymphocytic leukemia / small
lymphocytic lymphoma) based on the standard histologic and immunophenotypic criteria
described in the WHO classification of lymphoid malignancies, including
immunophenotypic confirmation that the tumor cells co-express B cell antigens CD19 /
20 and CD5. Mantle cell lymphoma should be excluded based on positive staining of
the tumor cells for CD23, or the absence of staining of the tumor cells for cyclin D1
or the absence of t(11;14).

- The above diagnosis must be confirmed at Brigham & Women's Hospital or Dana-Farber
Cancer Institute.

- Subjects must have relapsed after at least one prior fludarabine-containing regimen
and require treatment based on NCI-WG criteria (Appendix A).

- Subjects must have measurable disease (lymphocytosis > 5,000 / ml, or palpable
lymphadenopathy or CT measurable lymphadenopathy > 1.5 cm, or bone marrow involvement

- Men and women of reproductive potential must agree to use an acceptable method of
birth control during treatment and for six months after completion of treatment.

- Age >= 18

- WHO Performance status <= 2

- Subject has provided written informed consent.

- Expected survival > 3 months

Exclusion Criteria:

- History of HIV

- Active infection uncontrolled by appropriate antibacterial, antiviral or antifungal

- Known CNS involvement with CLL

- Pregnant (a negative serum pregnancy test should be performed for all women of
childbearing potential within 7 days of treatment) or currently lactating women

- Prior anti-neoplastic therapy within the last three weeks

- Patients will NOT be excluded because they have received prior rituximab or

Type of Study:


Study Design:

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

Outcome Measure:

Maximum tolerated dose of alemtuzumab given once weekly

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Jennifer R Brown, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

May 2006

Completion Date:

December 2014

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Chronic Lymphocytic Leukemia
  • Relapsed Chronic Lymphocytic Leukemia
  • Alemtuzumab
  • Campath
  • Rituximab
  • Rituxan
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Dana-Farber Cancer Institute Boston, Massachusetts  02115