Patients with B-cell chronic
lymphocytic leukemia (B-CLL) may soon have a more effective treatment
option earlier in the course of their disease, according to final data from
the CAM 307 international Phase III study presented today at the 48th
Annual Meeting of the American Society of Hematology.(1) These data showed
alemtuzumab (Campath(R), MabCampath(R)) was superior to chlorambucil as a
first-line therapy with respect to progression free survival (PFS) in
previously untreated patients with B-CLL. Patients receiving alemtuzumab
also exhibited higher overall and complete response rates with a manageable
safety profile, compared to patients who were treated with chlorambucil.
"This study demonstrates that alemtuzumab is superior as a first-line
therapy compared to chlorambucil," stated lead investigator Peter Hillmen,
M.B., Ch.B, Consultant Haematologist, Leeds General Infirmary, Leeds,
United Kingdom.
Results from the open-label, randomized trial showed that alemtuzumab
demonstrated a superior PFS versus chlorambucil (p = 0.0001), meeting the
study's primary endpoint, and the risk of progression or death was reduced
by 42 percent with alemtuzumab versus chlorambucil (p=0.0001). Of the 297
patients in the study, the overall response rate (ORR) for alemtuzumab was
83 percent versus 55 percent for chlorambucil (p < 0.0001), which
represents a nearly 30 percent greater ORR with alemtuzumab. The complete
response rate (CRR) was 24 percent for alemtuzumab versus two percent for
chlorambucil (p < 0.0001), representing a 12-fold higher CRR with
alemtuzumab. Chlorambucil is a chemotherapy drug that has been used
extensively in first-line treatment of B- CLL.
"We are very encouraged by the activity and safety of alemtuzumab as a
single-agent for the treatment of CLL. This study encourages us to fully
explore the potential of alemtuzumab in combination and consolidation
therapies," said Dr. Hillmen.
Nine of a total of 34 complete responder patients receiving alemtuzumab
achieved a minimal residual disease (MRD) negative response, as defined by
testing below the level of B-CLL detection. Eight out of these nine MRD
negative patients demonstrated a sustainable response showing no disease
progression at a median follow-up of two years following treatment. The
goal of MRD negativity was not achieved for any of the three patients
reaching a complete response with chlorambucil. Studies suggest that aiming
to reduce MRD below any detectable level is achievable and associated with
prolonged treatment-free and overall survival.
There were no significant differences observed in grade 3/4
thrombocytopenia (the presence of relatively few platelets in blood),
anemia (a deficiency of red blood cells and/or hemoglobin) or febrile
neutropenia (a condition in which patients have a fever and a low white
blood cell count). Statistically significant differences in the rates of
grade 3/4 neutropenia (a condition characterized by an abnormally low
number of a type of white blood cell known as neutrophil granulocytes),
between the alemtuzumab and chlorambucil patient groups were reported.
Among patients receiving alemtuzumab, the most common grade 3/4
treatment- related adverse events were infusion-related reactions
associated with intravenous administration, including fevers and chills.
Symptomatic CMV reactivation developed in only 16 percent of patients and
was managed with antiviral therapy. There were no treatment-related deaths
among patients receiving alemtuzumab, while one treatment-related death
occurred in a patient receiving chlorambucil.
About This Study
The open-label trial randomized 297 patients with previously untreated,
progressive disease requiring treatment at 44 medical centers in Europe and
the United States. Patients were treated with either 30 mg of alemtuzumab
IV three times per week for a maximum of 12 weeks, inclusive of dose
escalation periods, or 40 mg/m2 of chlorambucil PO once every 28 days to a
maximum of 12 cycles.
Progression-free survival was the primary endpoint, and secondary
endpoints included safety, overall and complete response rates, and overall
survival.
The study was sponsored by Genzyme Corporation and Schering AG. Leeds
General Infirmary was a CAM 307 clinical trial site.
About CLL
CLL is a type of cancer in which the bone marrow manufactures too many
lymphocytes (a type of white blood cell). Symptoms include enlarged lymph
nodes, liver or spleen, fatigue, abnormal bruising, excessive sweating,
loss of appetite, and weight loss. Patients are also susceptible to
weakening of the immune system, exposing the patient to a higher risk of
infection. CLL affects about 120,000 people in Europe and the US and is the
most prevalent form of adult leukemia. The disease often occurs during or
after middle age; it hardly ever occurs in children. In CLL, too many
functionally immature white blood cells (lymphocytes) accumulate in the
bone marrow, blood, lymph tissue, and other organs. There are two types of
lymphocytes present in the blood: B cells and T cells. About 95 percent of
CLL cases involve cancerous B cells. Because these B cells have a longer
than normal life span, they begin to build up, leaving less room for
healthy white blood cells, red blood cells, and platelets. The accumulation
of functionally immature cells in the bone marrow excludes the generation
of healthy cells and can become fatal.
(1) Hillmen et al. Alemtuzumab (CAMPATH(R), MABCAMPATH(R) Has Superior
Progression Free Survival (PFS) vs. Chlorambucil as Front-Line
Therapy for Patients with Progressive B-Cell Chronic Lymphocytic
Leukemia (B-CLL), Presented at the 48th Annual Meeting of the
American Society of Hematology 2006.
The Leeds Teaching Hospitals
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