T-PLL-1 Protocol of the German CLL Study Group (GCLLSG) - A Prospective Phase II Trial of Fludarabine Phosphate, Mitoxantrone and Cyclophosphamide (FMC) Followed by Alemtuzumab Consolidation in T-PLL.

Introduction: T-cell prolymphocytic leukemia (T-PLL) is an aggressive disease with a poor median overall survival of <12 months. With the introduction of alemtuzumab therapy, a response rate of 50% has been observed, including pretreated patients (

Patients and methods: From November 2001 to May 2005, 18 patients with T-PLL were entered into this prospective trial, 16 patients were evaluable to date. The median age of the patients was 65 years (range, 46– 73 years). All patients presented with typical hyperleukocytosis (median count = 167,000/L), and 5 patients had received prior therapy. Binet staging for the patients was as follows: A (n = 3), B (n = 4), and C (n = 9). The treatment schedule included 4 cycles of fludarabine phosphate (Fludara) 25 mg/m² on Days 1–3, mitoxantrone 8 mg/m² on Day 1, and cyclophosphamide 200 mg/m² on Days 1–3, (FMC) and repeated on Day 29. After 3 months of chemotherapy, all patients were scheduled to receive alemtuzumab 30 mg IV three times per week as consolidation therapy.

Results: To date, 40 cycles of FMC therapy and a total of 28 weeks of alemtuzumab therapy have been documented. Thirteen cases of grade 3 leukopenia, 7 cases of grade 4 leukopenia, 2 cases of grade 3 thrombocytopenia, and 6 cases of grade 4 thrombocytopenia were observed. The best responses to FMC therapy were 8 CR, 3 PR, 2 SD, and 3 PD. Seven of 8 patients who achieved a CR, and 2 of 3 patients who achieved a PR, received subsequent alemtuzumab as consolidation therapy. One of the 3 patients with PD received alemtuzumab consolidation, but the disease continued to progress. However, 2 patients with SD after FMC achieved a CR with alemtuzumab. One patient progressed and died after 2 FMC cycles. Another patient had continuous pancytopenia with bone marrow involvement, and therefore, was considered to have PD. Relapse occurred in 3 patients with CR after FMC and alemtuzumab therapies, and in 1 patient with SD after FMC treatment that had achieved a CR after alemtuzumab therapy. The overall response rates after FMC and alemtuzumab therapies were 68% and 90%, respectively. The median survival was 13.4 months and PFS was 10.6 months for 12 evaluable patients.

Conclusion: In conclusion, FMC is an effective regimen in the first-line treatment of T-PLL. Our trial indicates that the combination of a fludarabine phosphate-containing regimen with subsequent alemtuzumab therapy has the potential to be beneficial in the treatment of T-PLL. However, as relapses were observed after completing the schedule, an intensified first-line therapy followed by alemtuzumab maintenance therapy might be useful in the treatment of T-PLL. A study of FMC combined with alemtuzumab followed by an alemtuzumab maintenance therapy is currently under investigation.