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A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML

ConditionsAcute Myeloid LeukemiaMixed Lineage Leukemia Gene MutationRefractory AMLAML With Mutated NPM1Acute Myeloid Leukemia RecurrentAcute Myeloid Leukemia, in RelapseNPM1 MutationKMT2ArMyeloid SarcomaNucleophosmin 1-mutated Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorKura Oncology, Inc.

About this trial

Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with certain genetic alterations.

This protocol has 3 separate arms that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) drug treatments in patients who have AML with certain genetic mutations. Both newly diagnosed and relapsed refractory patients with AML will be assigned to different cohorts based on specific study criteria and physician discretion.

The purpose of this study is to assess the safety, tolerability, and early signs of efficacy of ziftomenib in combination with SOC drugs to treat AML.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML

Those intending treatment with intensive chemotherapy in Arm C should be NPM1-m and FLT3-ITD+ with an allelic ratio ≥0.05 and eligible for FLT3-targeted treatment

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Adequate liver, renal, and cardiac function according to protocol defined criteria

Disqualifiers

Diagnosis of either acute promyelocytic leukemia or blast phase chronic myeloid leukemia

Known history of BCR-ABL alteration

Advanced malignant hepatic tumor

Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ziftomenib

    Drug

    Oral Administration

  • Venetoclax

    Drug

    Oral Administration

  • Azacitidine

    Drug

    Subcutaneous or Intravenous Administration

  • Daunorubicin

    Drug

    Intravenous Administration

  • Cytarabine

    Drug

    Intravenous Administration

  • Quizartinib

    Drug

    Oral Administration

Treatment groups

420 Participants
are divided into 13 treatment groups

13

Treatment groups

See each treatment group below.

Group A: Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1)Experimental treatment 3 interventions
Group B: Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R NPM1-m (A-1)Experimental treatment 3 interventions
Group C: Dose Escalation: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2)Experimental treatment 3 interventions
Group D: Dose Validation/Expansion: Ziftomenib with 7+3 in 1L NPM1-m/FLT3 wildtype (A-2)Experimental treatment 3 interventions
Group E: Dose Validation/Expansion: Ziftomenib with Venetoclax in R/R NPM1-m (A-3)Experimental treatment 2 interventions
Group F: Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in 1L NPM1-m (A-4)Experimental treatment 3 interventions
Group G: Dose Escalation: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1)Experimental treatment 3 interventions
Group H: Dose Validation/Expansion: Ziftomenib with Venetoclax and Azacitidine in R/R KMT2A-r (B-1)Experimental treatment 3 interventions
Group I: Dose Escalation: Ziftomenib with 7+3 in 1L KMT2A-r (B-2)Experimental treatment 3 interventions
Group J: Dose Validation/Expansion: Ziftomenib with 7+3 in 1L KMT2A-r (B-2)Experimental treatment 3 interventions
Group K: Dose Validation/Expansion: Ziftomenib with Venetoclax + Azacitidine in 1L KMT2A-r (B-3)Experimental treatment 3 interventions
Group L: Dose Escalation: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1)Experimental treatment 4 interventions
Group M: Dose Validation/Expansion: Ziftomenib with 7+3+quizartinib in 1L NPM1-m/FLT3-ITD+ AML patients (C-1)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Rate of dose limiting toxicities (DLTs) per dose level (Part 1a only)

Assessed by the NCI-CTCAE v5.0

Time frame
During the first 28 days of ziftomenib in combination with SOC backbone treatment (1 cycle)
2

Descriptive statistics of adverse events

Assessed by the NCI-CTCAE v5.0

Time frame
From Cycle 1 Day 1 up to and including 28 days following the end of 36 months of treatment
3

Complete remission (CR) rate

Assessed by the ELN 2022 criteria

Time frame
Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first

Secondary outcomes

1

Composite Complete Remission (CRc)

Assessed by the ELN 2022 criteria

Time frame
Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first
2

Morphologic leukemia-free state (MLFS) rate

Assessed by the ELN 2022 criteria

Time frame
Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever comes first
3

Measurable residual disease (MRD)

Assessed by multiparameter flow cytometry (MFC) and/or molecular analysis (NGS, PCR)

Time frame
Until relapse, new anti-cancer therapy, death, or up to 36 months of treatment, whichever occurs first
4

Median OS

To assess overall survival of ziftomenib

Time frame
From Cycle 1 Day 1 to date of death from any cause, assessed up to 36 months of treatment

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Kura Oncology, Inc.

Lead sponsor

Source ClinicalTrials.gov
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