Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML

a study on Acute Myeloid Leukemia Leukemia Hematologic Neoplasms

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSD
Dates
study started
study ends around

Description

Summary

Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with eligible genetic alterations. Ziftomenib is a type of therapy known to target the menin pathway in cancer cells.

This protocol has 2 separate studies that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) AML treatments in patients with certain genetic mutations who have not received any treatment for their AML. In the first study, the Nonintensive Therapy Study, older patients or those with serious medical problems will receive the SOC therapies venetoclax (ven) and azacitidine (aza), plus either ziftomenib or a placebo. In the second study, the Intensive Therapy Study, medically fit patients will receive (a) the SOC therapies cytarabine and daunorubicin, plus either ziftomenib or a placebo during a first treatment phase called induction, (b) cytarabine plus either ziftomenib or a placebo during a second treatment phase called consolidation, and (c) ziftomenib or a placebo during a third treatment phase called maintenance.

The physician will determine which study is the appropriate treatment for the patient, but neither the patient nor their physician will know whether the patient has been assigned to receive ziftomenib or a placebo. This design is called "double-blinded".

Official Title

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 With Untreated NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia

Details

This protocol encompasses two phase 3, randomized, double-blind, placebo-controlled clinical studies to assess the efficacy, safety, and tolerability of ziftomenib in combination with: (a) the standard of care (SOC) nonintensive regimen (venetoclax [ven]+azacitidine [aza]) in untreated adults with nucleophosmin 1 mutated (NPM1-m) acute myeloid leukemia (AML); or (b) the SOC intensive regimen (cytarabine+daunorubicin induction, referred to here as 7+3, and cytarabine consolidation) in untreated adults with NPM1-m or lysine[K]-specific methyltransferase 2A rearranged (KMT2A-r) AML, as well as a maintenance phase.

Nonintensive Therapy Study (Ven+Aza)

Eligible NPM1-m patients will be enrolled and randomized to receive:

  • Arm A: Ziftomenib in combination with ven+aza or
  • Arm B: Placebo in combination with ven+aza.

Patients will be randomized to treatment arms in a double-blind manner.

Intensive Therapy Study (Cytarabine+Daunorubicin)

Eligible NPM1-m or KMT2A-r patients will be enrolled and randomized to 1 of the following treatment arms:

  • Arm A: Ziftomenib+7+3 (induction), ziftomenib+cytarabine (consolidation), ziftomenib (maintenance) or
  • Arm B: Ziftomenib+7+3 (induction), ziftomenib+cytarabine (consolidation), placebo (maintenance) or
  • Arm C: Placebo+7+3 (induction), placebo+cytarabine (consolidation), placebo (maintenance).

Patients will be randomized to treatment arms in a double-blind manner.

Keywords

Acute Myeloid Leukemia (AML), AML, Hematological malignancy, KMT2A, NPM1, Menin, Acute Leukemia, Leukemia, Acute Myeloid Leukemia, Newly diagnosed AML, Newly diagnosed KMT2A-r AML, Newly diagnosed NPM1m AML, Untreated AML, Untreated NPM1m AML, Untreated KMT2A-r AML, MLL, Leukemia, Myeloid, Acute, Hematologic Neoplasms, venetoclax, Azacitidine, Daunorubicin, Cytarabine, Ziftomenib, Azacitidine (AZA), Cytarabine (Ara-C)

Eligibility

You can join if…

Open to people ages 18 years and up

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:
        1. 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.

You CAN'T join if...

  • 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) >25×109/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.

Locations

  • University of California, San Diego accepting new patients
    La Jolla California 92093 United States
  • Texas Oncology - San Antonio Medical Center accepting new patients
    San Antonio Texas 78240 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Kura Oncology, Inc.
ID
NCT07007312
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 1300 study participants
Last Updated
Contact us about this trial