 OS in adult patients with newly diagnosed NPM1-mutated AML

ineligible for intensive chemotherapy, measured from the date of

randomization to the date of death from any cause.

 Rate of CR in adult patients with newly diagnosed NPM1-mutated

AML ineligible for intensive chemotherapy, defined as the

proportion of NPM1-mutated AML patients who achieve CR at

any time-point during protocol therapy.

 EFS in adult patients with newly diagnosed NPM1-mutated AML

ineligible for intensive chemotherapy, measured from the date of

randomization to the date of treatment failure, hematologic

relapse from CR/CRh (i.e., not molecular relapse) or death from

any cause, whichever occurs first; treatment failure in this unfit

AML population is defined as lack of obtaining either CR or CRh

by week 24.

 Rate of CR/CRh in adult patients with newly diagnosed NPM1-

mutated AML ineligible for intensive chemotherapy, defined as

the proportion of NPM1-mutated AML patients who achieve CR or

CRh at any time-point during protocol therapy.

1. Patient with newly diagnosed NPM1-mutated AML, consistent with NPM1c, according to the 2022

International Consensus Classification (i.e. ≥ 10% blasts).

OR

Patient with newly diagnosed KMT2A-rearranged AML according to the 2022 International

Consensus Classification (i.e. ≥ 10% blasts). KMT2A partial tandem duplications or deletions are

NOT eligible.

Of note: in case both NPM1 and IDH1 are mutated and both EVOLVE-1 (HO173) and EVOLVE-2

(HO177) are open for inclusion at your site, then patients can only be included in the EVOLVE-1

trial (HO173)

2. Central confirmation of NPM1 mutation or KMT2A rearrangement in one of the dedicated central

genetic laboratories.

3. Age ≥ 18 years, no upper age limit.

4. Patient is ineligible for intensive induction chemotherapy by meeting at least 1 of the following

criteria:

1. Patient has previously been treated for AML; a treatment period with hydroxyurea to control WBC

counts is allowed; prior treatment with a hypomethylating agent for MDS-EB is not allowed; prior

treatment with erythropoiesis-stimulating agents or luspatercept for MDS is allowed.

2. Acute promyelocytic leukemia (APL) with t(15;17)(q24.1;q21.2); PML-RARA; or one of the other

pathognomonic variant chromosomal translocations / fusion genes.

3. AML with BCR-ABL1; or myeloid blast crisis of CML