Azacitidine, Lenalidomide and DLI as Salvage Therapy for MDS, CMML and sAML Relapsing After Allo-HSCT

Overview

This is a prospective, open-label, single-arm multi-center phase II study aiming to evaluate the safety and feasibility of the addition of Lenalidomide (investigational drug) to the standard therapy of Azacitidine and DLI (standard of care) as first salvage therapy for relapse of MDS, CMML and AML with MDS-related changes (sAML, with 20%-30% bone marrow blasts, formerly RAEB-T) after allo-SCT. The starting dose of Lenalidomid is 2.5 mg per day for 21 days with a 7 day rest. The study incorporates 2 interim safety analyses after 10 and 20 patients in order to find the optimal and safe dose of Lenalidomide.

This is a prospective, open-label, single-arm multi-center phase II study aiming to evaluate the safety and feasibility of the addition of Lenalidomide (investigational drug) to the standard therapy of Azacitidine and DLI (standard of care) as first salvage therapy for relapse of MDS, CMML and AML with MDS-related changes (sAML, with 20%-30% bone marrow blasts, formerly RAEB-T) after allo-SCT. Study Design: * prospective, open-label, single arm, multicenter phase-II trial * total patients sample size: 50 patients * number of trial sites: 6 all located in Germany and members of the EBMT Patients will be included at the time of relapse after first allo-SCT. Starting on day 1 all patients will receive Azacitidine 75 mg/m2/d for 7 days every 28 days for up to 8 cycles. DLIs will be given after cycle 4, 6 and 8. Lenalidomide will be also started on day 1 for 21 days every 28 days for a maximum of 8 cycles. The concomitant administration of Aza and Lenalidomide will be used since safety and efficacy of this schedule has been demonstrated. Azacitidine and DLI represent a standard of care in this setting and are therefore not considered as investigational. As 5-Azacytidine is given in-label, treatment may be continued beyond 8 cycles. Additional DLIs may be given according to the investigators choice. However, to avoid severe GvHD it is recommended to give at least one more cycle 5-Azacytidine after additional DLIs. The study incorporates a dose escalating schedule for Lenalidomide and two safety interim analyses. A first interim analysis will be performed as soon as 10 patients have been treated with Lenalidomide at a dose of 2.5mg/day If no dose limiting toxicity is observed in this cohort the next cohort of 10 patients will be treated with 5 mg per day for 21 days starting on day 1. If dose limiting toxicity occurs the study will be closed. A second interim analysis will be performed as soon as 10 patients have been treated with Lenalidomide at a dose of 5mg/day and the 10th patient of this cohort has either completed 4 cycles or has discontinued treatment whichever occurs first. If no dose limiting toxicity is observed in this cohort, the dose of 5 mg per day for 21 days starting on day 1 will be chosen and the remaining patients will be treated with this dose of Lenalidomide. If dose limiting toxicity occurs in patients treated with 5mg per day the remaining patients will be treated with Lenalidomide at a dose of 2.5mg/day. A total number of 50 patients will be treated. Independent of the dose level, Lenalidomide will be stopped individually in the case of GvHD ≥ grade II.