Figure 1.
Study design and treatment. ∗For de-escalation to dose level –1 in arm C, patients received CPX-351 induction and consolidation at dose level 1 combined with enasidenib 100 mg on days 8 to 21. †Patients could have received up to 2 induction courses in total at the discretion of the treating investigator. A second induction was highly recommended for any patient with no response or documented reduction in leukemia burden. If safe to administer, a second induction was mandatory for patients who achieved >50% reduction in the percentage of blasts count in their BM assessment during the first induction on day 14 for arm A and on day 21 for arms B and C. ‡During the first induction, to mitigate the risk of potential tumor lysis syndrome, a dose ramp-up of venetoclax was administered from 100 mg/d on day 1 to 200 mg/d on day 2, and then 400 mg/d (target dose) on days 3 to 14. For subsequent inductions or consolidations, venetoclax was administered at the full target dose (400 mg on days 1 to 14). Based on previous PK studies, concomitant treatment with a strong CYP3A inhibitor was permitted after the venetoclax dose ramp-up with a dose reduction of venetoclax by 75%, whereas concomitant treatment with a moderate CYP3A inhibitor was permitted after the venetoclax dose ramp-up with a dose reduction of venetoclax by 50%. §Coadministration of midostaurin with strong CYP3A inhibitors may increase midostaurin concentrations, with increase more pronounced in the first week of midostaurin administration, and this may increase the risk of midostaurin-associated toxicity. Alternative therapies that do not strongly inhibit CYP3A activity were recommended. Alternatively, with coadministration of midostaurin and strong CYP3A inhibitors, monitoring patients for increased risk of adverse reactions, especially during the first week of midostaurin administration in each course of therapy was recommended. ¶Patients who achieved remission (CR, CRi, or CRh), neutrophils ≥0.5 × 109/L, and platelets ≥50 × 109/L could have received up to 2 consolidation courses at the discretion of the treating investigator. BID, twice daily; CYP, cytochrome P450 enzymes; ITD, internal tandem duplication; TKD, tyrosine kinase domain; WT, wild type.

Study design and treatment. ∗For de-escalation to dose level –1 in arm C, patients received CPX-351 induction and consolidation at dose level 1 combined with enasidenib 100 mg on days 8 to 21. †Patients could have received up to 2 induction courses in total at the discretion of the treating investigator. A second induction was highly recommended for any patient with no response or documented reduction in leukemia burden. If safe to administer, a second induction was mandatory for patients who achieved >50% reduction in the percentage of blasts count in their BM assessment during the first induction on day 14 for arm A and on day 21 for arms B and C. ‡During the first induction, to mitigate the risk of potential tumor lysis syndrome, a dose ramp-up of venetoclax was administered from 100 mg/d on day 1 to 200 mg/d on day 2, and then 400 mg/d (target dose) on days 3 to 14. For subsequent inductions or consolidations, venetoclax was administered at the full target dose (400 mg on days 1 to 14). Based on previous PK studies, concomitant treatment with a strong CYP3A inhibitor was permitted after the venetoclax dose ramp-up with a dose reduction of venetoclax by 75%, whereas concomitant treatment with a moderate CYP3A inhibitor was permitted after the venetoclax dose ramp-up with a dose reduction of venetoclax by 50%. §Coadministration of midostaurin with strong CYP3A inhibitors may increase midostaurin concentrations, with increase more pronounced in the first week of midostaurin administration, and this may increase the risk of midostaurin-associated toxicity. Alternative therapies that do not strongly inhibit CYP3A activity were recommended. Alternatively, with coadministration of midostaurin and strong CYP3A inhibitors, monitoring patients for increased risk of adverse reactions, especially during the first week of midostaurin administration in each course of therapy was recommended. ¶Patients who achieved remission (CR, CRi, or CRh), neutrophils ≥0.5 × 109/L, and platelets ≥50 × 109/L could have received up to 2 consolidation courses at the discretion of the treating investigator. BID, twice daily; CYP, cytochrome P450 enzymes; ITD, internal tandem duplication; TKD, tyrosine kinase domain; WT, wild type.

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