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(Drug information on 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 advanced CLL.