Treatment-free Remission After Nilotinib for Chronic Myeloid Leukemia

(ENESTop Trial)

Recruiting at 68 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

163 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if it is safe for chronic myeloid leukemia (CML) patients to stop taking their medication. The study focuses on patients who initially started with one medication and then switched to another for a significant period. Researchers want to see if these patients can keep their leukemia under control without continuing the medication.

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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