212 Participants Needed

Ziftomenib Combinations for Acute Myeloid Leukemia

Recruiting at 50 trial locations
CO
Overseen ByClinical Operations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are in the relapsed/refractory cohort, you should not have received chemotherapy, immunotherapy, or investigational therapy within 14 days before starting the trial.

Is the combination of Ziftomenib and other drugs safe for treating acute myeloid leukemia?

The combination of venetoclax and azacitidine has been studied for safety in patients with acute myeloid leukemia, showing that while it can cause some serious side effects like low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and low red blood cell counts (anemia), these side effects are generally considered tolerable.12345

What makes the Ziftomenib combination drug unique for treating acute myeloid leukemia?

The Ziftomenib combination drug is unique because it includes Ziftomenib, a novel component not commonly used in standard treatments for acute myeloid leukemia. This combination also incorporates venetoclax and azacitidine, which have shown improved remission rates and survival in older or unfit patients compared to azacitidine alone.24567

What evidence supports the effectiveness of the drug combination including Ziftomenib for treating acute myeloid leukemia?

Research shows that combining venetoclax with azacitidine improves remission rates and survival in patients with acute myeloid leukemia, especially those who are older or not fit for intensive chemotherapy. This suggests that similar drug combinations, like those including Ziftomenib, may also be effective.12789

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of leukemia (AML) that's either new or has come back after treatment. They must have certain genetic changes (NPM1 mutation or KMT2A rearrangement), be in decent physical shape, and agree to use birth control. People can't join if they have other active cancers, uncontrolled infections, heart problems, CNS involvement by AML, high white blood cell counts without management options like hydroxyurea or leukapheresis, HIV/Hepatitis B/C infection, or if women are pregnant/breastfeeding.

Inclusion Criteria

I agree to use birth control or abstain from sex as required.
My liver, kidneys, and heart are working well.
My AML is either new or has returned, and tests show I have an NPM1 mutation or KMT2A rearrangement.
See 1 more

Exclusion Criteria

I have a known BCR-ABL gene change.
Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF) >480 ms on triplicate ECGs
I have not received any live vaccines within the last 14 days and won't until my B-cell levels recover.
See 12 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ziftomenib in combination with venetoclax/azacitidine, venetoclax, or 7+3 chemotherapy

28 days per cycle, multiple cycles
Regular visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Long-term follow-up

Participants are assessed for overall survival and other long-term outcomes

Up to 1 year following end of treatment

What Are the Treatments Tested in This Trial?

Interventions

  • Azacitidine
  • Cytarabine
  • Daunorubicin
  • Venetoclax
  • Ziftomenib
Trial Overview The study tests the safety and potential effectiveness of Ziftomenib combined with Venetoclax/Azacitidine ('ven/aza'), just Venetoclax ('ven'), or standard chemo ('7+3') in patients with Acute Myeloid Leukemia (AML). It focuses on those who have NPM1 mutations or KMT2A rearrangements.
How Is the Trial Designed?
11Treatment groups
Experimental Treatment
Group I: Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)Experimental Treatment3 Interventions
Group II: Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)Experimental Treatment3 Interventions
Group III: Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L NPM1-m (A-4)Experimental Treatment3 Interventions
Group IV: Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L KMT2A-r (B-3)Experimental Treatment3 Interventions
Group V: Dose Validation/Expansion: Ziftomenib/Venetoclax in R/R NPM1-m (A-3)Experimental Treatment2 Interventions
Group VI: Dose Validation/Expansion: Ziftomenib/7+3 in 1L NPM1-m (A-2)Experimental Treatment3 Interventions
Group VII: Dose Validation/Expansion: Ziftomenib/7+3 in 1L KMT2A-r (B-2)Experimental Treatment3 Interventions
Group VIII: Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)Experimental Treatment3 Interventions
Group IX: Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)Experimental Treatment3 Interventions
Group X: Dose Escalation: Ziftomenib/7+3 in 1L NPM1-m (A-2)Experimental Treatment3 Interventions
Group XI: Dose Escalation: Ziftomenib/7+3 in 1L KMT2A-r (B-2)Experimental Treatment3 Interventions

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

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Approved in European Union as Vidaza for:
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Approved in United States as Vidaza for:
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Approved in Canada as Vidaza for:
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Approved in Japan as Vidaza for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Kura Oncology, Inc.

Lead Sponsor

Trials
19
Recruited
1,700+

Published Research Related to This Trial

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.
The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.
Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia.Kadia, TM., Reville, PK., Wang, X., et al.[2023]
The combination of venetoclax (Ven) and azacitidine (AZA) shows a high efficacy in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), with an overall complete response rate of 57.9% across 19 studies involving 1615 patients.
This treatment is particularly effective for newly diagnosed AML patients, achieving a complete response rate of 67.5%, although it is less effective for those with relapsed or refractory AML, which had a response rate of only 30%.
The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis.Du, Y., Li, C., Yan, J.[2023]
In a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.
The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.
Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy.Yamamoto, K., Shinagawa, A., DiNardo, CD., et al.[2023]

Citations

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. [2023]
The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis. [2023]
Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. [2023]
[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. [2023]
Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML. [2021]
[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. [2022]
SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. [2023]
Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial. [2022]
Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. [2022]
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