Phase II Study of Rituximab and Cladribine (2-CDA) in Newly Diagnosed Mantle Cell Lymphoma (MCL) (N0189).

Background: A previous trial of 2-CDA as a single agent for therapy of mantle cell lymphoma demonstrated this agent to be efficacious with an overall response rate of 81% (31% complete responses) (Blood 1999 Nov 15; 94:660a). A phase II study of the addition of rituximab to 2-CDA was conducted by the North Central Cancer Treatment Group based on improved outcomes achieved by the addition of rituximab to other regimens active in MCL.

Methods: This one-stage phase II study was designed to determine the complete response (CR) or complete response/unconfirmed (CRu) rate. Central pathology confirmation of cyclin D1 positive mantle cell lymphoma was required. No previous therapy for lymphoma was allowed, with the exception of splenectomy. The schedule was rituximab 375 mg/m2 IV day 1; 2-CDA 5 mg/m2/d IV days 1–5 of a 4-week cycle. After 2 of the first 6 patients developed grade 4 neutropenia, subsequent patients received either pegfilgrastim or filgrastim support. Patients received 2–6 cycles of therapy, depending on response. Patients were required to achieve at least a PR after 2 cycles of therapy to continue on protocol therapy.

Results: Patient characteristics of all 29 eligible pts: median age: 70 (range: 41–86); 21 male, 8 female; PS 0 (55.2%), PS 1 (41.4%), PS 2 (3.5%); stage II (6.9%), stage III (3.5%), stage IV (89.7%); prior splenectomy (20.7%). The only grade 4 adverse events occurring more than once were neutropenia (24.1%) and leucopenia (6.9%). One patient died of cerebral ischemia in the setting of pneumonia without neutropenia. Fifteen (51.7%; 95% CI: 32.5–70.6%) pts achieved a CR; only one has relapsed to date (665 days after starting therapy). Four additional pts achieved a PR. Ten pts have progressed with 4 pts progressing early at 17, 45, 46, and 71 days (two of whom have died). Ten pts (34.0%) went on to receive further therapy off study, 5 in less than a PR after 2 cycles, 2 in PR after study therapy, and 1 who went off study for a rash. Fourteen pts (48.3%) have progressed or gone on to receive additional therapy off study. At last contact, 26 (89.7%) were alive (median follow-up 14.3 months; range: 6–34). One year survival rate is 89.3% (95% CI: 78.5–100).

Conclusions: Rituximab and cladribine were well tolerated for the treatment of MCL in a group of elderly patients. The response rate may have been underestimated due to the study design, which required at least a PR after 2 cycles to continue therapy. Despite this, 52% achieved a complete remission. Complete remissions attained with this regimen appear to be durable, with a single relapse to date among 15 patients achieving CR.