What side effects are associated with this type of intervention?

Common treatments for acute leukemia, such as hypomethylating agents (HMAs) like azacitidine and decitabine, often have side effects including myelosuppression (leading to neutropenia, anemia, and thrombocytopenia), gastrointestinal symptoms (nausea, vomiting, diarrhea), and fatigue. Other treatments, such as targeted therapies and chemotherapy, can also cause similar hematologic toxicities, as well as additional side effects like infections, liver function abnormalities, and mucositis. For treatments similar to Ziftomenib, specific side effects are not detailed, but they may share common adverse effects with other targeted therapies, including cytopenias and gastrointestinal disturbances.

What prior FDA approvals exist?

The FDA has approved several treatments for acute leukemia, including hypomethylating agents like azacitidine and decitabine, which are commonly used for newly diagnosed AML in older adults or those unfit for intensive chemotherapy. Additionally, targeted therapies such as venetoclax (a BCL-2 inhibitor) and ivosidenib (an IDH1 inhibitor) have shown efficacy when combined with HMAs. These treatments are somewhat related to the investigational menin-MLL(KMT2A) inhibitor ziftomenib, as they all represent targeted approaches to treating specific genetic or molecular subtypes of acute leukemia.

What other types of research exist?

Promising novel alternatives to Ziftomenib for Acute Leukemia patients include: 1) HMA (hypomethylating agents) plus venetoclax, which has shown improved outcomes compared to HMA monotherapy. 2) HMA plus ivosidenib, which is another combination that has demonstrated benefits. 3) Decitabine with sapacitabine, which has shown similar outcomes to decitabine alone but may offer an alternative approach. 4) Azacitidine plus gilteritinib, which has shown a higher overall response rate compared to azacitidine plus placebo.

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Menin-MLL(KMT2A) Inhibitor

Ziftomenib for Relapsed/Refractory Acute Myeloid Leukemia

Q: What is the mechanism of action of this treatment?

The most common treatments for Acute Leukemia include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, which includes cancer cells, but also affects normal cells, leading to significant side effects. Targeted therapies, such as Ziftomenib (a Menin-MLL(KMT2A) inhibitor), specifically inhibit molecular abnormalities driving the leukemia, offering a more precise approach with potentially fewer side effects. Immunotherapy leverages the body's immune system to recognize and destroy cancer cells. These mechanisms are crucial for Acute Leukemia patients as they provide options that can be tailored to the genetic and molecular profile of their disease, potentially improving outcomes and reducing toxicity.

Phase 1 & 2

Recruiting

Research Sponsored by Kura Oncology, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with refractory or relapsed AML defined as the reappearance of ≥ 5% blasts in the bone marrow and who have also failed or are ineligible for any approved standard of care therapies, including HSCT.

Phase 1b: Patients with a documented lysine[K]-specific methyltransferase 2-rearrangement (KMT2A-r), or Patients with a documented nucleophosmin 1 mutation (NPM1-m)

Must not have

Not recovered to < Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline.

Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 months following end of treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ziftomenib, a new drug, in patients with difficult-to-treat acute myeloid leukemia (AML). The drug works by blocking a protein interaction that cancer cells need to grow.

Who is the study for?

Adults with relapsed or refractory acute myeloid leukemia (AML) who have failed standard treatments can join this trial. They must have controlled white blood cell counts, be in relatively good health, and agree to use effective contraception. People with active central nervous system leukemia, recent heart issues, uncontrolled infections, or those on certain drugs that affect liver enzymes are excluded.

What is being tested?

The study is testing Ziftomenib's safety and effectiveness for AML patients whose disease has returned or hasn't responded to treatment. It's a two-phase trial: the first phase adjusts doses; the second expands testing specifically to patients with an NPM1 mutation.

What are the potential side effects?

As this is a first-in-human study of Ziftomenib, side effects are being closely monitored but may include typical chemotherapy-related symptoms such as fatigue, nausea, increased risk of infection due to lowered immunity, liver and kidney function changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My AML has returned or didn't respond to treatment, and I can't have or failed standard treatments.

Select...

My cancer has a specific genetic change (KMT2A-r or NPM1-m).

Select...

I can care for myself and doctors expect me to live at least 2 more months.

Select...

My cancer has a NPM1 mutation.

Select...

I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have recovered from major side effects of previous treatments.

Select...

I am on immunosuppressive therapy after a stem cell transplant.

Select...

I have not received a donor lymphocyte infusion in the last 30 days.

Select...

I do not have serious heart problems or a stroke in the last 6 months.

Select...

I have a condition that increases my risk of serious infections.

Select...

I have not had major surgery in the last 4 weeks.

Select...

I had a stem cell transplant but my blood counts haven't recovered.

Select...

I haven't had any experimental treatments in the last 14 days or within 5 half-lives before starting ziftomenib.

Select...

I do not have any active, uncontrolled infections.

Select...

I am experiencing moderate to severe symptoms from a transplant complication.

Select...

My leukemia is affecting my brain or spinal cord.

Select...

I have been diagnosed with acute promyelocytic leukemia.

Select...

My condition is advanced chronic myelogenous leukemia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 months following end of treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 months following end of treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 months following end of treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1a: Maximal tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D)

Phase 1b: Minimal biologically effective dose

Phase 1b: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs).

+1 more

Secondary study objectives

Phase 1a: AUC(0-last)

Phase 1a: Cmax

Phase 1a: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs).

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase 2Experimental Treatment1 Intervention

NPM1-m patients will receive the recommended phase 2 dose determined in Phase 1

Group II: Phase 1b - Dose-Validation ExpansionExperimental Treatment1 Intervention

Cohort 1: KMT2A-r / NPM1-m patients will receive a dose previously studied in Phase 1a Cohort 2: KMT2A-r / NPM1-m patients will receive a dose previously studied in Phase 1a

Group III: Phase 1a - Dose EscalationExperimental Treatment1 Intervention

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Acute Leukemia include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, which includes cancer cells, but also affects normal cells, leading to significant side effects. Targeted therapies, such as Ziftomenib (a Menin-MLL(KMT2A) inhibitor), specifically inhibit molecular abnormalities driving the leukemia, offering a more precise approach with potentially fewer side effects. Immunotherapy leverages the body's immune system to recognize and destroy cancer cells. These mechanisms are crucial for Acute Leukemia patients as they provide options that can be tailored to the genetic and molecular profile of their disease, potentially improving outcomes and reducing toxicity.

Immunotherapy in AML: a brief review on emerging strategies.Progress in the problem of relapsed or refractory acute myeloid leukemia.Molecular targeting in acute myeloid leukemia.