What side effects are associated with this type of intervention?

Common treatments for Myeloid Leukemia, such as hypomethylating agents (azacitidine and decitabine) and targeted therapies (ivosidenib and venetoclax), have several known side effects. Azacitidine and decitabine can cause cytopenias, gastrointestinal symptoms, and injection site reactions. Ivosidenib, used for IDH1-mutated AML, may lead to differentiation syndrome, QTc prolongation, and fatigue. Venetoclax, often combined with HMAs, can result in neutropenia, infections, and tumor lysis syndrome. These side effects are important considerations when selecting a treatment plan.

What prior FDA approvals exist?

Asciminib is a novel STAMP inhibitor targeting the ABL myristoyl pocket, specifically studied for Chronic Myeloid Leukemia (CML). Similar FDA-approved treatments for Myeloid Leukemia include tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib, which target the BCR-ABL fusion protein. These TKIs have been pivotal in the treatment of CML by inhibiting the abnormal tyrosine kinase activity that drives the disease. Additionally, other treatments like hypomethylating agents (e.g., azacitidine and decitabine) and targeted therapies (e.g., venetoclax) have been approved for various forms of Myeloid Leukemia, offering a range of options based on the specific genetic and molecular characteristics of the disease.

What other types of research exist?

Promising novel alternatives to Asciminib for Myeloid Leukemia patients include: 1) Venetoclax in combination with hypomethylating agents (HMAs) such as azacitidine or decitabine, which has shown improved outcomes in clinical trials. 2) Ivosidenib for patients with IDH1 mutations, which has demonstrated efficacy in combination with HMAs. 3) Gilteritinib, a FLT3 inhibitor, which can be used in combination with azacitidine for patients with FLT3 mutations. These alternatives have shown potential in clinical trials and may offer effective treatment options for Myeloid Leukemia patients in 2024.

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Tyrosine Kinase Inhibitor

Asciminib Combinations for Chronic Myeloid Leukemia (ALERTCML Trial)

Phase 2

Recruiting

Led By Jorge Cortes, MD

Research Sponsored by Augusta University

Eligibility Criteria Checklist

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

Must have

Adequate organ function: AST and ALT < 3 times the institutional upper limit of normal (ULN), Creatinine < 1.5 times the institutional upper limit of normal, Total bilirubin < 1.5 times the institutional ULN or < 3.0 x the institutional ULN with Gilbert Syndrome (unless direct bilirubin is within normal limits), Adequately controlled blood pressure, defined as systolic blood pressure of <140 mmHq and diastolic of <90 mmHg, at the time of enrollment, Serum lipase less than or equal to 1.5 x ULN. For serum lipase > ULN - less than or equal to 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis.

Age ≥18 years old

Must not have

Patient has undergone a prior allogeneic stem cell transplant

Patients with accelerated or blast phase CML

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the effectiveness and safety of a medication called asciminib in patients newly diagnosed with Chronic Myeloid Leukemia in the Chronic Phase. Patients will take asciminib daily, and if they do not respond after a few years, they may also take another low-dose medication. Asciminib works by blocking a protein that helps cancer cells grow.

Who is the study for?

Adults over 18 with newly diagnosed Chronic Myeloid Leukemia in chronic phase, who have not been treated for more than 30 days. They must have normal organ function and agree to effective contraception. Excluded are those with advanced CML stages, other active cancers, recent pancreatitis, certain blood disorders or taking strong CYP3A4 inhibitors/inducers.

What is being tested?

The trial is testing the safety and effectiveness of asciminib as an initial oral treatment for new Chronic Myeloid Leukemia patients. If no response after up to 36 months, a low dose of dasatinib, imatinib or nilotinib may be added at the doctor's choice.

What are the potential side effects?

Possible side effects include digestive issues (like pancreatitis), changes in blood counts leading to increased infection risk or bleeding problems, liver enzyme alterations and potential interactions with other drugs metabolized by specific liver enzymes.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I can take care of myself and perform daily activities.

Exclusion Criteria

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

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I have had a stem cell transplant from a donor.

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My CML is in the accelerated or blast phase.

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I have been treated with asciminib before.

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I have had pancreatitis in the last year.

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I am not taking any strong medication that affects liver enzymes.

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I am currently being treated for another type of cancer.

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I have had serious heart issues or abnormal heart rhythms in the past 6 months.

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I have an active hepatitis B infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Measure 1: Deep Molecular Response

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: AsciminibExperimental Treatment4 Interventions

Asciminib 80mg taken orally once a day starting cycle 1 day 1 for up to 24 months during the single agent asciminib phase. Patients who have not achieved MR4.5 after 24 months will be given a low dose tyrosine kinase inhibitor (low-TKI). There will be three options of low-TKIs to be given at the investigator's discretion.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Asciminib

2018

Completed Phase 1

~570

0 / 11Eligibility 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 Myeloid Leukemia include hypomethylating agents (HMAs) like azacitidine and decitabine, which work by inhibiting DNA methylation, thereby reactivating tumor suppressor genes and inducing cancer cell death. Tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib target the BCR-ABL fusion protein, a result of the Philadelphia chromosome abnormality, inhibiting its kinase activity and preventing leukemic cell proliferation. Asciminib, a STAMP inhibitor, targets the ABL myristoyl pocket, offering a novel mechanism to inhibit BCR-ABL activity. These treatments are crucial as they specifically target the molecular abnormalities driving Myeloid Leukemia, leading to more effective and personalized therapy options for patients.

Basic science going clinical: molecularly targeted therapy of chronic myelogenous leukemia.Targeting treatment in AML.Targeted chronic myeloid leukemia therapy: seeking a cure.