Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML

Table 1 Glasdegib interruptions in case of toxicities

Toxicity causing glasdegib interruption	Resumption within the first 21 days when:
Any toxicity grade ≥3 according to CTCAE criteria potentially attributable to glasdegib regardless of when it occurs in the cycle.	Toxicity returns to patient’s baseline/ toxicity resolved (non-hematological toxicity recovers to grade ≤1)
ANC < 0.1G/l and /or platelets <10G/l regardless of when it occurs in the cycle	ANC ≥0.1G/l and platelet count ≥10G/l and re-treatment can occur safely as per the investigator’s judgment
No resolution of above toxicities after 21 days	Discontinue medication permanently

Glasdegib doses omitted for toxicity are not replaced within that cycle (e.g., cycles are not to be prolonged beyond 28 days in order to make up for any missed glasdegib doses during that cycle). Toxicity is graded according to CTCAE criteria. Once the Glasdegib dose has been reduced, all subsequent cycles should be administered at that dose level, unless further dose reduction is required. Dose re-escalation is not allowed. Abbreviations: CTCAE Common Terminology Criteria for Adverse Events, ANC absolute neutrophil count.

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