Treatment-free Remission After Nilotinib for Chronic Myeloid Leukemia

(ENESTop Trial)

No longer recruiting at 83 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Tyrosine kinase inhibitors

Must not be taking: CYP3A4 inhibitors, QT prolonging drugs

Disqualifiers: Cardiac issues, Uncontrolled diabetes, Pancreatitis, 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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether people with chronic myeloid leukemia (CML) can safely stop taking the medication nilotinib (also known as Tasigna). The goal is to determine if patients, treated with specific medications for at least three years and having very few leukemia cells left, can maintain their health without ongoing treatment. This trial suits those who have switched from imatinib to nilotinib and have been on nilotinib for at least two years, with a very low level of leukemia cells remaining. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications to join the trial. If you are taking strong CYP3A4 inhibitors or inducers, herbal medicines like St. John's Wort, or medications that prolong the QT interval, you must either discontinue them or switch to different medications before starting the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that nilotinib is generally well-tolerated by people with chronic myeloid leukemia (CML). Studies have found it effective and safe for both adults and children. For instance, a study in Korea found that adult patients using nilotinib did well and benefited from the drug in regular medical settings. Another study found no treatment-related deaths in children over about five years, supporting its long-term safety.

Additionally, a study in Greece examined how patients managed with nilotinib in everyday medical practice. It confirmed that the drug is safe and easy for patients to handle. This is encouraging for those considering joining a clinical trial involving nilotinib.

Nilotinib is already approved to treat CML, indicating that its safety has been well-studied. While all medications can have side effects, nilotinib's safety is better understood than many experimental treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CML?

Most treatments for Chronic Myeloid Leukemia (CML) involve continuous use of tyrosine kinase inhibitors like imatinib, which patients typically need to take indefinitely to keep the disease in check. However, nilotinib is unique because it offers the potential for treatment-free remission. This means that patients who have achieved a deep molecular response (MR4.5) with nilotinib might be able to stop medication entirely while maintaining remission. Researchers are excited about nilotinib because it targets the cancer cells more precisely and could improve quality of life by reducing or eliminating the need for ongoing medication.

What evidence suggests that stopping nilotinib might be safe for chronic myeloid leukemia patients?

Studies have shown that nilotinib can be effective for patients with chronic myeloid leukemia (CML) who wish to stop treatment and remain in remission. In this trial, researchers will assess participants who have taken nilotinib for at least two years and achieved a deep molecular response for treatment-free remission. Research indicates that about 80% of patients who reach a deep molecular response (a very low level of leukemia cells) can stay in remission after stopping nilotinib. Another study found that nearly half of the patients who reduced their nilotinib dosage remained in remission without the disease returning. Importantly, no patients attempting to stop treatment died from CML-related issues, and the disease did not worsen. This suggests that nilotinib could be a reliable option for CML patients considering stopping treatment while maintaining remission. ^{6 7 8 9 10}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults diagnosed with chronic myeloid leukemia (CML) who have been treated first with imatinib for over 4 weeks, then switched to nilotinib for at least 2 years, totaling a minimum of 3 years of treatment. They must show very low levels of leukemia cells after nilotinib treatment and meet specific health criteria like normal organ function and blood counts.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I have been diagnosed with chronic myeloid leukemia in the chronic phase.

I've been treated with specific cancer drugs for over 3 years since my diagnosis.

Exclusion Criteria

Known impaired cardiac function including any one of the following: Inability to determine the QT interval on ECG, Complete left bundle branch block, Long QT syndrome or a known family history of long QT syndrome, History of or presence of clinically significant ventricular or atrial tachyarrhythmias, Clinically significant resting bradycardia, QTcF > 480 msec, History or clinical signs of myocardial infarction within 1 year prior to study entry, History of unstable angina within 1 year prior to study entry, Other clinically significant heart disease (e.g. uncontrolled congestive heart failure or uncontrolled hypertension), Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes (defined as HbA1c > 9%), uncontrolled infection), History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis, Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer, History of other active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ treated curatively, Patients who have not recovered from prior surgery, Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1, Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry, Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry, Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to study entry, Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery), Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test, Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test before initiation of study treatment and must also use highly effective methods of contraception while enrolled in the study.

I switched from imatinib to nilotinib with a MR4.5 status.

My cancer has a known unusual genetic change.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Nilotinib Treatment Consolidation Phase (NTCS)

Patients receive nilotinib for 52 weeks to maintain MR4.5 before entering the TFR phase

52 weeks

Nilotinib Treatment-Free Remission Phase (TFR)

Patients stop taking nilotinib and are monitored for up to 520 weeks for treatment-free remission

520 weeks

Nilotinib Treatment Re-initiation Phase (NTRI)

Patients who lose MR4 or MMR during TFR phase restart nilotinib treatment

Up to 520 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Post-treatment follow-up visits every 12 weeks up to 520 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nilotinib

Trial Overview The study is testing the safety of stopping the drug nilotinib in CML patients who have responded well to it. It aims to see if these patients can maintain their health without continuing the medication after achieving a significant reduction in leukemia cells.

How Is the Trial Designed?

Group I: Nilotinib Experimental Treatment 1 Intervention

Patients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening

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

Approved in European Union as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in United States as Tasigna for:

• Chronic phase (CP) and accelerated phase (AP) Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in adult patients resistant to or intolerant to prior therapy that included imatinib

Approved in Canada as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in Japan as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

Approved in Switzerland as Tasigna for:

• Chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including imatinib

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12248582/

Real-World Evidence of Treatment-Free Remission ... The vast majority of prospective trials indicate that no patients who have trialed TFR have died a CML-related death, with disease progression ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hon.70126

Treatment‐Free Remission in Chronic Phase ... Fifty-two of the 107 patients who entered the nilotinib de-escalation phase (48.6%) remained in sustained DMR from the de-escalation phase until ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01784068

Nilotinib Treatment-free Remission Study in CML (Chronic ... The main purpose of the study was to investigate whether nilotinib treatment can be safely suspended with no recurrence of CML in selected patients.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6566

Long-term follow-up of treatment-free remission in chronic ... The long-term follow-up results continue to demonstrate improved TFR rates of approximately 80% in patients who achieve a deep molecular response (MR4 or ...

5. haematologica.org haematologica.org/article/view/10596

10-year followup of the GIMEMA CML 0307 study The use of nilotinib front-line in chronic phase chronic myeloid leukemia can induce a stable treatment-free remission in a relevant number of patients.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0268960X2200042X

Long-term safety review of tyrosine kinase inhibitors in ... This review summarizes the safety profiles of the currently approved TKIs and how they impact treatment selection in the first- and later-line settings of CML.

7. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/tasigna

Tasigna | European Medicines Agency (EMA) Tasigna is a medicine for treating chronic myelogenous leukaemia (CML) – a blood cancer – in patients who have been newly diagnosed or who cannot take other ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9242833/

Safety and efficacy of nilotinib in adult patients with chronic ... Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings. Keywords: Nilotinib, ...

9. ashpublications.org ashpublications.org/bloodadvances/article/7/23/7279/497976/The-long-term-efficacy-and-safety-of-nilotinib-in

The long-term efficacy and safety of nilotinib in pediatric ... No on-treatment deaths occurred. These long-term (up to ∼5 years) data support the efficacy and safety of nilotinib in pediatric patients with ...

10. scientificarchives.com scientificarchives.com/article/safety-and-tolerability-of-nilotinib-in-patients-with-chronic-myeloid-leukemia-during-routine-clinical-practice-results-from-the-eraser-study-from-greece

Safety and Tolerability of Nilotinib in Patients with Chronic ... This multicenter, observational, prospective study, ERASER, evaluated the safety and tolerability of nilotinib in routine clinical practice in Greece.