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

作者：Terakura S^*; Atsuta Y; Sawa M; Ohashi H; Kato T; Nishiwaki S; Imahashi N; Yasuda T; Murata M; Miyamura K; Suzuki R; Naoe T; Ito T; Morishita Y

来源：Annals of Oncology, 2011, 22(8): 1865-1871.

DOI：10.1093/annonc/mdq673

• allogeneic bone marrow transplantation
• dose-finding study
• modified continual reassessment method
• reduced-intensity conditioning

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 and methods: The conditioning regimen consisted of i.v. fludarabine (125 mg/m(2)) 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/m(2). 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/m(2) (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/m(2) was determined as the recommended phase II dose to induce initial full-donor chimerism.

• 出版日期2011-8