Asciminib + Imatinib for Chronic Myeloid Leukemia

No longer recruiting at 41 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Imatinib

Must not be taking: Other TKIs

Disqualifiers: Uncontrolled diabetes, Pancreatitis, ECG abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of medications to evaluate their effectiveness and safety for people with chronic myeloid leukemia in the chronic phase (a type of blood cancer). It compares different doses of two drugs, asciminib (also known as Scemblix) and imatinib, against each other and another treatment, nilotinib. The goal is to determine which treatment is most effective for patients who have been on imatinib for at least a year without achieving a deep molecular response (a specific level of cancer cell reduction). This trial suits those diagnosed with chronic myeloid leukemia in the chronic phase who have been treated with imatinib but need better cancer control. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires participants to have been on imatinib for at least one year before joining, so you will need to continue taking imatinib. The protocol does not specify if you need to stop any other medications, so it's best to discuss this with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that patients generally tolerate the combination of asciminib and imatinib well. Previous studies found that this combination had fewer side effects than some other treatments. The most common side effects were mild, such as headaches and tiredness.

Imatinib alone has long been used to treat chronic myeloid leukemia (CML) and is considered relatively safe. Some patients might experience mild side effects like nausea or muscle cramps.

Nilotinib has proven effective, but it can cause more serious side effects. Some patients have experienced higher blood sugar levels or heart problems, though these are uncommon.

Overall, the treatments in this trial have been tested in people before, and their safety is well-documented. While side effects can occur, they are generally known and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Chronic Myeloid Leukemia (CML) because asciminib has a novel mechanism of action. Unlike other treatments that primarily target the BCR-ABL1 protein, asciminib specifically targets the ABL myristoyl pocket, offering a new approach to inhibit cancer cell growth. This unique action allows it to be combined with imatinib, potentially enhancing effectiveness without increasing toxicity. This combination could present a more effective treatment option, particularly for patients who have not responded well to standard therapies like imatinib or nilotinib alone.

What evidence suggests that this trial's treatments could be effective for Chronic Myeloid Leukemia?

This trial will evaluate the effectiveness of different treatment combinations for chronic myeloid leukemia (CML). Studies have shown that combining asciminib with imatinib can effectively treat CML. Research indicates that adding asciminib to imatinib helps more patients achieve a deep molecular response, significantly reducing cancer cells. Specifically, asciminib has demonstrated better results compared to some other treatments, with patients experiencing improved outcomes. For those who don't respond well to imatinib alone, this combination could offer new hope. These findings make asciminib a promising option for those with CML in the chronic phase. Participants in this trial may receive either the combination of asciminib and imatinib or imatinib alone, while others may receive nilotinib as a comparator. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Chronic Myeloid Leukemia in chronic phase (CML-CP) who have been treated with imatinib for at least a year and haven't achieved deep molecular response. They must meet specific blood, liver, and kidney health criteria. Excluded are those with heart issues, history of pancreatitis or other cancers within the last 3 years, or previous treatment failures on imatinib.

Inclusion Criteria

Patient must meet specific laboratory values before randomization: Absolute Neutrophil Count ≥ 1.5 x 10E9/L, Platelets ≥ 75 x 10E9/L, Hemoglobin ≥ 9 g/dL, Serum creatinine < 1.5 mg/dL, Total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's syndrome), Aspartate transaminase (AST) ≤ 3.0 x ULN, Alanine transaminase (ALT) ≤ 3.0 x ULN, Alkaline phosphatase ≤ 2.5 x ULN, Serum lipase ≤ 1.5 x ULN. Patients must have other laboratory values within normal limits or corrected with supplements prior to randomization.

I have been treated with imatinib for at least a year for my CML-CP.

In Korea, I've been treated with imatinib for at least 1 or 2 years based on my BCR-ABL levels.

Exclusion Criteria

History or current diagnosis of ECG abnormalities indicating significant risk or safety for subjects participating in the study

I haven't had any other cancer besides this one in the last 3 years.

I have been treated with a tyrosine kinase inhibitor other than imatinib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized treatment with asciminib in combination with imatinib, continued imatinib, or switch to nilotinib for up to 96 weeks

96 weeks

Cross-over

Participants on the imatinib continuation arm who have not achieved MR4.5 at 48 weeks may cross-over to receive asciminib 60 mg combination add-on treatment

4 weeks after week 48

Follow-up

Participants are monitored for safety for 30 days after the last dose received

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib
• Imatinib
• Nilotinib

Trial Overview The study tests the effectiveness and safety of adding Asciminib to Imatinib versus continuing only Imatinib or switching to Nilotinib or using Asciminib alone in patients previously treated for CML-CP. It also examines how these drugs interact within the body.

How Is the Trial Designed?

Group I: Asciminib 60mg QD + Imatinib 400mg QD Experimental Treatment 2 Interventions

Asciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily

Group II: Asciminib 40mg QD + Imatinib 400mg QD Experimental Treatment 2 Interventions

Asciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily

Group III: Imatinib 400mg QD Active Control 1 Intervention

Imatinib 400 mg taken once daily

Group IV: Nilotinib 300mg BID Active Control 1 Intervention

Nilotinib 300 mg taken twice daily

Asciminib is already approved in United States, European Union for the following indications:

Approved in United States as Scemblix for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults previously treated with ≥2 tyrosine kinase inhibitors (TKIs)
• Ph+ CML in CP with the T315I mutation
• newly diagnosed Ph+ CML in CP

Approved in European Union as Scemblix for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults previously treated with ≥2 tyrosine kinase inhibitors (TKIs)
• Ph+ CML in CP with the T315I mutation

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2400858

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia In this trial comparing asciminib with investigator-selected TKIs and imatinib, asciminib showed superior efficacy and a favorable safety ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11657281/

Asciminib add-on to imatinib demonstrates sustained high ... Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03578367?term=ASCIMINIB&viewType=Table&rank=7

Study of Efficacy and Safety of Asciminib in Combination ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

4. scemblix-hcp.com scemblix-hcp.com/efficacy/clinical-trial-results

Clinical Trial Results | SCEMBLIX® (asciminib) Analyze the clinical trial results for SCEMBLIX® (asciminib) for adult patients with newly diagnosed Ph+ CML-CP. See full Prescribing and Safety ...

5. novartis.com novartis.com/news/media-releases/longer-term-data-novartis-scemblix-reinforce-superior-efficacy-favorable-safety-and-tolerability-profile-adults-newly-diagnosed-cml

Longer-term data for Novartis Scemblix® reinforce superior ... Combination Therapy Using Asciminib Plus Imatinib (IMA) in Patients (PTS) with Chronic Myeloid Leukemia (CML): Results from a Phase 1 Study.

6. ashpublications.org ashpublications.org/blood/article/144/19/1993/517275/Asciminib-monotherapy-as-frontline-treatment-of

Asciminib monotherapy as frontline treatment of chronic ... Key PointsAsciminib monotherapy leads to high rates of early and major molecular response in newly diagnosed chronic-phase CML.Safety and ...