Ziftomenib in Combination With Nonintensive or Intensive Therapy in Acute Myeloid Leukemia

What is the Purpose of this Study?

This study focuses on people with acute myeloid leukemia (AML) and consists of 2 independent studies/ treatment regimens. AML is a type of blood cancer in which infection-fighting cells (white blood cells) do not mature like they are supposed to and stay stuck as infant or immature “blast” cells. Participants in this study will need to have AML blast cells that have a mutation in the NPM1 gene, without FLT3, or rearrangement in the KMT2A gene. One treatment option is nonintensive therapy (usually for older patients or those with serious medical problems), such as a combination of 2 drugs called venetoclax and azacitidine (ven/aza). AML can also be treated with targeted therapy, which works by targeting specific mutations in cancer cells. Part of this study will investigate the potential risks and benefits of adding a targeted experimental therapy called ziftomenib to nonintensive therapy (ven/aza). The other part of this study (intensive therapy) will evaluate the potential risks and benefits of adding ziftomenib to 7+3 induction (a common chemotherapy treatment regimen for AML), as well as intensive therapy with cytarabine consolidation (a type of leukemia treatment) and determining whether the use of ziftomenib as maintenance therapy following consolidation is beneficial in people with AML. Study procedures include exams, lab work, electrocardiogram, echocardiogram, lumbar puncture, bone-marrow biopsy, questionnaires, and taking the study drug or placebo (inactive substance).

Eligibility

The following criteria apply to both the Nonintensive Therapy Study and the Intensive Therapy Study unless otherwise noted:
* Age ≥18 years at time of signing the informed consent form.
* Diagnosis of AML per the 2022 WHO Classification of Hematolymphoid Tumors (5th Edition).

Key Inclusion Criteria:

The following criteria apply to both the Nonintensive Therapy Study and the Intensive Therapy Study unless otherwise noted:
* Age ≥18 years at time of signing the informed consent form.
* Diagnosis of AML per the 2022 WHO Classification of Hematolymphoid Tumors (5th Edition).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Adequate liver and kidney function according to protocol requirements.
* A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male with a female partner of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention.
* NONINTENSIVE THERAPY STUDY ONLY (VEN+AZA):
1. Documented NPM1-m.
2. Patients considered ineligible for Intensive Therapy defined by the following:
* i. Age ≥75, OR
* ii. Age \<75 with an ECOG performance status of 2 or cardiac, renal, or kidney impairment per protocol criteria.
* INTENSIVE THERAPY STUDY ONLY (7+3):
1. Documented NPM1-m or KMT2A-r (KMT2A-r patients with a partial tandem duplication are not eligible).
2. Documented FLT3 wild-type or ITD ratio \<0.05 OR ineligible to receive FLT3-targeted therapy (medically ineligible or mutation in which FLT3 inhibition is not SOC). Lack of access to an FLT3 inhibitor is not considered "ineligible" for FLT3-targeted therapy.
3. Ejection fraction of ≥50%.
4. Fit for Intensive Therapy per Investigator opinion.

Key Exclusion Criteria:

* Prior therapy for AML (except hydroxyurea or leukapheresis for WBC control).
* Diagnosis of acute promyelocytic leukemia (APL), blast phase chronic myeloid leukemia, or isolated myeloid sarcoma.
* Known history of BCR-ABL mutation.
* History of other active concurrent malignancies prior to study entry except:
1. Basal cell skin cancer or localized squamous cell cancer of the skin
2. Previous malignancy confined and locally resected (or treated with other modalities) with curative intent
3. Prostate or breast cancer receiving adjuvant hormonal therapy.
* Active central nervous system (CNS) involvement by AML.
* Clinical signs/symptoms of leukostasis or white blood cells (WBC) \>25×10\^9/L prior to start of ziftomenib/placebo. Note: Hydroxyurea and/or leukapheresis are permitted to meet this criterion.
* Known uncontrolled HIV infection or known active hepatitis B virus, hepatitis C virus infection, or other uncontrolled infection.
* Uncontrolled intercurrent illness including but not limited to, cardiac illness as defined in the protocol.
* Women who are pregnant or lactating.

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Where can I participate?

CS Cancer at Beverly Hills : Emilie Douine-Barthelemy
CS Cancer at Cedars-Sinai Medical Center : Emilie Douine-Barthelemy

More about this Clinical Trial

What is the full name of this clinical trial?

KO-MEN-017: Phase 3 Randomized, Double-blind, Placebo-controlled Studies Assessing Ziftomenib in Combination with Either Standard of Care Nonintensive or Intensive Therapy in Patients with Untreated NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia

Study Details

Disease Type/Condition

Leukemia, not otherwise specified

Principal Investigator

Merin, Noah

Co-Investigators

Akil Merchant, David Oveisi, Hannah Lee, Hitomi Hosoya, Jeremy Lorber, Joshua Sasine, Justin Darrah, Lawrence Liu, Robert Vescio, Ronald Paquette

Age Group

Adult

Phase

III

IRB Number

STUDY00004323

ClinicalTrials.gov ID

NCT07007312

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Emilie Douine-Barthelemy

emilie.douine-barthelemy@cshs.org