52 Because of its unique mechanism of action, and a defined dose-limiting toxicity of neutropenia in solid tumors, sapacitabine became an attractive agent to investigate in hematological malignancies.
If patients experienced significant toxicity other than the defined dose limiting events, treatment was delayed until recovery to grade 0 1, and then restarted, for the subsequent cycles, at the dose level below.
Maximum tolerated dose was based on defined dose-limiting toxicities (DLTs) during therapy and 2 weeks post therapy.
Dosing used a 6+6 phase 1 dose escalation design, with the first six patients accrued at DL 0, and subsequent DL's determined according to evaluation of defined dose-limiting toxicities (DLTs) (Supplementary Table 1; Supplementary Figure 1).
AE, SAE, SADR and SUSAR will be monitored for 35 days and evaluated by an independent safety board to define any dose limiting toxicity (DLT).
The clinician must specify the required dose to be delivered to the target volume and also define the dose limits for the organs at risk.
Dose-limiting toxicity (DLT) was defined as any ⩾grade 3 event at any time up to 4 weeks after treatment, except for neutropaenia which was defined as dose-limiting only when being grade IV, with neutropaenic fever, with neutropaenic infection or when it occurred in the first 14 days (capecitabine only) of treatment.
The primary endpoint is the occurrence of a dose limiting toxicity defined as any Grade IV toxicity according to CTCAE Version 4.1, possibly, probably or definitely associated to study treatment and occurring within 3 months after completion of the study treatment.
The primary endpoint is the occurrence of a dose limiting toxicity defined as any Grade IV toxicity according to CTCAE Version 4.0, possibly, probably or definitely associated to study treatment and occurring during 30 days after completion of the study treatment.
Bendamustine, an active alkylating agent in lymphoma and chronic lymphocytic leukemia, was given in a fractionated twice daily schedule for 4 days to patients with acute leukemia and myelodysplastic syndrome (MDS) to define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD).
