 In case dose limited toxicity DLT was seen in a subject, further dosing of subjects in the same dose group will be discussed with the DSMB, in case of a second DLT in the same dose group dose escalation will be stopped and the study will be continued at the next lower intermediate dose level or the previous tested dose will be regarded as the maximum tolerated dose MTD. The MTD is defined as the dose level below the dose inducing a DLT in 2 subjects within one dose level. 