Phase 3 Randomized, Double-blind, Placebo-controlled Studies Assessing Ziftomenib in Combination with Either Standard of Care Nonintensive (Venetoclax+Azacitidine) or Intensive (7+3) Therapy in Patients Untreated NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia

Cancer Categories

Hematologic (Blood Cancers)

Karmanos Trial ID

2025-049

NCT ID

NCT07007312

Age Group

Adult

Scope

National

Phase

Phase III

Principal Investigator

Suresh
Balasubramanian, M.D.
Oncology - Hematology, Oncology - Medical View Profile

Objective:

Nonintensive Therapy Study (Ven+Aza)

Primary Objectives:

To evaluate the effect of ziftomenib combined with SOC ven+aza on patient survival in untreated NPM1-m AML
To determine the efficacy of ziftomenib combined with SOC ven+aza in untreated NPM1-m AML

Secondary Objectives:

To determine the rate of MRD negativity achieved with ziftomenib combined with SOC ven+aza in untreated NPM1-m AML
To evaluate CR/CRh as an additional measure of efficacy of ziftomenib in combination with SOC ven+aza in untreated NPM1-m AML
To evaluate additional measures of efficacy of ziftomenib in combination with SOC ven+aza in untreated NPM1-m AML
To characterize the safety and tolerability of ziftomenib in combination with SOC ven+aza in untreated NPM1-m AML
To characterize the PK of ziftomenib and ven in the setting of SOC ven+aza in untreated NPM1-m AML
To evaluate if ziftomenib in combination with SOC ven+aza improves fatigue, physical functioning, role functioning, and tolerability based on PRO measures in untreated NPM1-m AML

Intensive Therapy Study (7+3)

Primary Objectives:

To evaluate the effect of ziftomenib combined with SOC 7+3 on patient EFS in untreated NPM1-m and KMT2A-r AML
To determine the efficacy of ziftomenib combined with SOC 7+3 in untreated NPM1-m AML

Secondary Objectives:

To evaluate the effect of ziftomenib combined with SOC 7+3 on patient survival in untreated NPM1-m and KMT2A-r AML
To evaluate additional measures of clinical activity of ziftomenib combined with SOC 7+3 in untreated NPM1-m and KMT2A-r AML
To characterize the safety and tolerability of ziftomenib in combination with SOC 7+3 in untreated NPM1-m and KMT2A-r AML
To characterize the PK of ziftomenib when administered with SOC 7+3 in untreated NPM1-m and KMT2A-r AML
To evaluate if ziftomenib in combination with SOC 7+3 improves fatigue, physical functioning, role functioning, and tolerability based on PRO measures in untreated NPM1-m and KMT2A-r AML

Request an Appointment

Refer a Patient

NCI Dictionary of Cancer Terms

KCI Clinical Trials App

Eligibility

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):

Documented NPM1-m.
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):

Documented NPM1-m or KMT2A-r (KMT2A-r patients with a partial tandem duplication are not eligible).
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.
Ejection fraction of ≥50%.
Fit for Intensive Therapy per Investigator opinion.

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:

Basal cell skin cancer or localized squamous cell cancer of the skin
Previous malignancy confined and locally resected (or treated with other modalities) with curative intent
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.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
Get Directions

Phone: 1-800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
Get Directions

Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices