Alemtuzumab and @entity39561 Chemotherapy for the Treatment of XXXX : A Multi-Center Phase I Study.

@entity1 @entity632 @entity137 @entity882 @entity2905 @entity229 @entity3191 @entity786 @entity364 @entity39561 @entity1891 @entity378
BACKGROUND: Alemtuzumab has single-agent activity in relapsed @entity3191 ( @entity3191 ), but the optimal dose and/or schedule in combination with chemotherapy for first-line use is unknown. The primary objectives were to establish the maximally tolerated dose and pharmacokinetics (PK) of alemtuzumab combined in this way. @entity1 AND METHODS: Adult @entity1 with untreated CD52-positive (CD52(+)) @entity3191 were enrolled in a phase I trial. Alemtuzumab was given subcutaneously in escalating doses and/or schedules in combination with @entity39561 ( @entity786 , @entity632 , @entity1891 and @entity229 ) using a 3+3 design. Trough PK of alemtuzumab were measured on day 1 of each 21-day cycle and B and T cell subsets were serially measured. RESULTS: Twenty @entity1 were enrolled across 4 dose levels. Dose-limiting @entity137 necessitated expansion at 10 mg weekly (fatal @entity378 ) and 60 mg every 3 weeks (grade 4 @entity882 ) dose levels. Maximally tolerated dose was not reached. Ten @entity1 developed asymptomatic cytomegalovirus reactivations at a median of 39 days (range, 4-99 days). Two @entity1 developed @entity364 . The overall and complete response rates were 68% and 37%, respectively. Highest day 1 alemtuzumab trough levels were achieved at 60 mg (1973 ng/mL), but with significant inter- and intradose variability. @entity2905 at baseline was common and  T cell recovery was significantly delayed. CONCLUSION: With monitoring and prophylaxis, alemtuzumab 60 mg combined with @entity39561 showed activity in CD52(+) @entity3191 and achieved the highest drug levels.
