A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies.
Ann Oncol
; 22(8): 1865-71, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21289367
ABSTRACT
BACKGROUND:
Because of the less graft-facilitating effect by bone marrow (BM), we need to assess a dosage of conditioning more accurately particularly in combination with reduced-intensity conditioning. Thus we examined that modified continual reassessment method (mCRM) is applicable for deciding appropriate conditioning of allogeneic BM transplantation. PATIENTS ANDMETHODS:
The conditioning regimen consisted of i.v. fludarabine (125 mg/m2) plus an examination dose of i.v. melphalan. The primary endpoint was a donor-type T-cell chimerism at day 28 with successful engraftment defined as >90% donor cells. Five patients per dose level were planned to be accrued and chimerism data were used to determine the next dose.RESULTS:
Seventeen patients were enrolled at doses between 130 and 160 mg/m2. The dose was changed from 160 to 130 mg/m(2) (second level) after five full-donor chimerisms. With one patient of 0% chimera in the second level, the dose was increased to 135 mg/m2 (third level). Following five full-donor chimerisms in the third level, the study was complete as projected.CONCLUSIONS:
mCRM was shown to be a relevant method for dose-finding of conditioning regimen. The melphalan dose of 135 mg/m2 was determined as the recommended phase II dose to induce initial full-donor chimerism.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vidarabina
/
Transplante de Medula Óssea
/
Neoplasias Hematológicas
/
Condicionamento Pré-Transplante
/
Agonistas Mieloablativos
/
Quimerismo
/
Melfalan
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Ann Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Japão