Alemtuzumab and CHOP Chemotherapy for the Treatment of Aggressive Histology Peripheral T Cell Lymphomas: A Multi-Center Phase I Study.
Clin Lymphoma Myeloma Leuk
; 16(1): 18-28.e4, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-26711181
ABSTRACT
BACKGROUND:
Alemtuzumab has single-agent activity in relapsed peripheral T cell lymphoma (PTL), 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. PATIENTS ANDMETHODS:
Adult patients with untreated CD52-positive (CD52(+)) PTL were enrolled in a phase I trial. Alemtuzumab was given subcutaneously in escalating doses and/or schedules in combination with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) 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 patients were enrolled across 4 dose levels. Dose-limiting toxicities necessitated expansion at 10 mg weekly (fatal tuberculosis reactivation) and 60 mg every 3 weeks (grade 4 thrombocytopenia) dose levels. Maximally tolerated dose was not reached. Ten patients developed asymptomatic cytomegalovirus reactivations at a median of 39 days (range, 4-99 days). Two patients developed fungal pneumonias. 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. Lymphopenia at baseline was common and T cell recovery was significantly delayed.CONCLUSION:
With monitoring and prophylaxis, alemtuzumab 60 mg combined with CHOP showed activity in CD52(+) PTL and achieved the highest drug levels.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Linfoma de Células T Periférico
/
Anticuerpos Monoclonales Humanizados
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Antineoplásicos
Tipo de estudio:
Clinical_trials
Idioma:
En
Revista:
Clin Lymphoma Myeloma Leuk
Asunto de la revista:
NEOPLASIAS
Año:
2016
Tipo del documento:
Article