12 Participants Needed

Entrectinib + ASTX727 for Acute Myeloid Leukemia

Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: OHSU Knight Cancer Institute
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 trial tests a combination of two medications for patients with a tough-to-treat type of leukemia. One drug stops cancer cells from growing, while the other helps make healthy blood cells and kills bad ones. The goal is to find the best dose and see if this combination is safe and effective.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have taken an investigational drug recently, you may need to wait before starting the trial.

Is the combination of Entrectinib and ASTX727 safe for humans?

The combination of cedazuridine and decitabine (ASTX727) has been studied for safety in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia, showing similar safety profiles to standard treatments. Common serious side effects included low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and fever with low white blood cell counts (febrile neutropenia).12345

What makes the drug combination of Entrectinib and ASTX727 unique for treating acute myeloid leukemia?

The combination of Entrectinib and ASTX727 for acute myeloid leukemia is unique because it combines a targeted therapy (Entrectinib) with a hypomethylating agent (ASTX727, which includes Decitabine and Cedazuridine) to potentially enhance treatment effectiveness by targeting specific cancer pathways and improving drug absorption.678910

What data supports the effectiveness of the drug combination Entrectinib + ASTX727 for Acute Myeloid Leukemia?

The research does not provide direct evidence for the effectiveness of Entrectinib + ASTX727 in treating Acute Myeloid Leukemia, but it mentions that hypomethylating agents like decitabine, which is part of ASTX727, are often used in AML treatment, suggesting potential relevance.68101112

Who Is on the Research Team?

Ronan Swords, M.D., Ph.D., FRCPI ...

Ronan T. Swords

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

Adults with relapsed/refractory AML and a TP53 mutation can join this trial. They must understand the study, be able to take oral meds, have decent organ function, and use contraception. Excluded are those with certain leukemia types, active infections like HIV or hepatitis B/C, uncontrolled diseases, recent investigational drugs usage or conditions affecting drug absorption.

Inclusion Criteria

My kidney function is within the required range.
My AML has a confirmed TP53 mutation.
My AML has returned or didn't respond to treatment, with at least 20% cancer cells in my blood or bone marrow.
See 9 more

Exclusion Criteria

I haven't taken any experimental drugs recently or still have side effects from one.
I have taken entrectinib for another cancer, but not decitabine.
I have symptoms of leukostasis that didn't improve after 3 days of urgent treatment.
See 11 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive entrectinib orally once daily on days 1-28 and ASTX727 orally once daily on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle
Cycle 1: 4 visits (in-person) on Day 1, Day 8, Day 28; subsequent cycles as needed

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 3 months for up to 1 year.

12 months
Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

  • Cedazuridine
  • Decitabine
  • Entrectinib
Trial Overview The trial is testing entrectinib combined with ASTX727 (cedazuridine plus decitabine) for safety and effectiveness in AML patients. Entrectinib blocks cancer cell growth signals; cedazuridine increases decitabine's availability which helps produce normal blood cells and kills abnormal ones.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (ASTX727, entrectinib)Experimental Treatment3 Interventions

Cedazuridine is already approved in United States for the following indications:

🇺🇸
Approved in United States as ASTX727 for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials
239
Recruited
2,089,000+

Genentech, Inc.

Industry Sponsor

Trials
1,578
Recruited
569,000+
Ashley Magargee profile image

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway profile image

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Taiho Oncology, Inc.

Industry Sponsor

Trials
79
Recruited
12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Taiho Oncology

Collaborator

Trials
2
Recruited
30+

Oregon Health and Science University

Collaborator

Trials
1,024
Recruited
7,420,000+

Published Research Related to This Trial

The BCL2 inhibitor venetoclax, when combined with low-dose cytarabine or hypomethylating agents, is both safe and effective for older patients with newly diagnosed acute myeloid leukemia (AML) who cannot undergo intensive chemotherapy.
New targeted therapies, such as glasdegib and CPX-351, have shown improved survival rates in specific patient populations, highlighting the importance of genomic characterization in selecting the most effective treatment for AML.
Single-agent and combination biologics in acute myeloid leukemia.Richard-Carpentier, G., DiNardo, CD.[2022]
In a phase 3 trial involving 319 patients aged 60 and older with relapsed/refractory acute myeloid leukemia (AML), enasidenib, an oral IDH2 inhibitor, showed significant improvements in event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI) compared to conventional care regimens.
Although the primary endpoint of overall survival (OS) did not show a significant difference between enasidenib and conventional care (6.5 vs 6.2 months), enasidenib demonstrated meaningful clinical benefits in a heavily pretreated population, suggesting its potential as an effective treatment option for older patients with mutant-IDH2 AML.
Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial.de Botton, S., Montesinos, P., Schuh, AC., et al.[2023]
Acute myeloid leukemia (AML) treatment has seen little change in 40 years, but new agents like IDH inhibitors and antibody-drug conjugates show promise in improving outcomes, either alone or with traditional chemotherapy.
A variety of novel therapies, including cytotoxic agents, epigenetic modifiers, and targeted inhibitors, are currently being tested in clinical trials, indicating a potential shift in AML management strategies.
Emerging therapies for acute myeloid leukemia.Saygin, C., Carraway, HE.[2023]

Citations

Single-agent and combination biologics in acute myeloid leukemia. [2022]
Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial. [2023]
Emerging therapies for acute myeloid leukemia. [2023]
Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial. [2023]
Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. [2019]
The path to approval for oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes. [2022]
Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. [2021]
[Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia]. [2019]
Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. [2019]
Glasdegib for the treatment of adult patients with newly diagnosed acute myeloid leukemia or high-grade myelodysplastic syndrome who are elderly or otherwise unfit for standard induction chemotherapy. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
What to use to treat AML: the role of emerging therapies. [2022]
Update on glasdegib in acute myeloid leukemia - broadening horizons of Hedgehog pathway inhibitors. [2023]
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