Campath-1H is a humanized anti-CD52 monoclonal
antibody, which has demonstrated marked activity against advanced,
refractory CLL. This multicenter phase II clinical trial sought to
establish the level of activity against CLL patients exposed to
alkylating agents and refractory to fludarabine (Fludara), a group
with an extremely poor prognosis. All patients had no response to or
had relapsed in < 6 months from the end of a fludarabine regimen.
Campath-1H (30 mg) was administered over 2 hours intravenously (IV)
three times weekly for 4 to 12 weeks after premedication with
acetaminophen and antihistamines and prophylactic cotrimoxazole and
famciclovir (Famvir) during and for 2 months after the study. An
independent panel using National Cancer Institute (NCI) criteria
(revised version, 1996) confirmed the diagnosis and responses.
Patients were enrolled over 4 months in the United States and Europe.
Median age was 66 years (range, 32 to 86 years), and 79% of patients
were male. The median number of prior treatments was three (range,
two to seven). Rai stage 3-4 disease was present in 76% of patients
and B symptoms in 30%.
Of the 93 patients, 92 were eligible for study (1 patient had
relapsed > 6 months after the last fludarabine dose), and 56
received the full course of Campath-1H therapy as planned. The
overall intent-to-treat response rate was 33% (95% confidence
interval [CI], 24% to 43%) with 2 (2%) complete responses (CRs), 29
(31%) partial responses (PRs), and 55 (59%) patients with stable
disease (SD). SD patients had antitumor responses in blood (97%),
nodes (62%), liver (73%), and spleen (71%). Responses were least
common in patients with bulky disease, females, and those with high
beta-2-microglobulin levels. With a median follow-up of 9 months, 26
(28%) patients have died, 9 due to infections (5 of which were
considered to be possibly related to Campath-1H therapy). The
projected median time to progression of responders is 9+ months, with 22/31
patients still in remission.
The most common adverse effects were fever and rigors (89%), nausea
and vomiting (50%), rash (33%), fatigue (29%), and dyspnea (24%); the
vast majority of these were of grade 1 or 2 severity. Neutropenia and
thrombocytopenia occurred in half of the patients and usually
improved within 1 to 2 months after discontinuing therapy. Anemia was
not a consistent problem.
Infection occurred in 56% of patients; one-third were grade 3 to 5
infections, such as pneumonia (5%), cytomegalovirus infections (2%),
Candida infections (2%), septicemia (2%), and others (4%).
Pneumocystis carinii infection occurred in two patients. Most
infections occurred during the first 2 months of therapy.
CONCLUSION: Campath-1H is an effective and relatively safe drug in
this population of high-risk, fludarabine-refractory patients with