What side effects are associated with this type of intervention?

Common treatments for leukemia, particularly Tyrosine Kinase Inhibitors (TKIs) like Nilotinib and Imatinib, are associated with several side effects. These include cytopenias (low blood cell counts), hepatotoxicity (liver damage), QTc prolongation (heart rhythm changes), and pancreatitis. Long-term use can lead to cardiovascular complications. Other side effects may include fatigue, gastrointestinal symptoms, and skin rashes. Chemotherapy, another common treatment, can cause nausea, vomiting, hair loss, and increased risk of infections due to bone marrow suppression.

What prior FDA approvals exist?

The FDA has approved several tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML), targeting the BCR-ABL fusion protein. Imatinib was the first TKI approved, revolutionizing CML treatment. Following imatinib, second-generation TKIs such as dasatinib, nilotinib, and bosutinib received FDA approval, offering alternatives for patients with resistance or intolerance to imatinib. These drugs have significantly improved outcomes for CML patients by specifically targeting the molecular abnormality driving the disease.

What other types of research exist?

Promising alternatives to discontinuation of Nilotinib for leukemia patients include other TKIs such as Dasatinib and Bosutinib, which have shown efficacy in patients with resistance or intolerance to previous TKI therapy. Additionally, newer agents like Asciminib, a STAMP inhibitor targeting the ABL myristoyl pocket, are emerging as effective options. These alternatives offer different mechanisms of action and may provide better tolerability and efficacy for certain patient populations.

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Tyrosine Kinase Inhibitor

Treatment-free Remission After Nilotinib for Chronic Myeloid Leukemia (ENESTop Trial)

Phase 2

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

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

Must have

ECOG Performance Status of 0, 1, or 2

Patient with diagnosis of BCR-ABL positive CML CP

Must not have

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.

Patient has documented MR4.5 at the time when switched from imatinib to nilotinib

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years following nilotinib cessation

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not specified here, common side effects from taking nilotinib may include headache, fatigue, nausea, rash, muscle pain, itching or other skin problems. Stopping treatment could potentially lead to an increase in white blood cell count as the body adjusts.

Eligibility Criteria

Inclusion Criteria

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

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

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

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

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I have been treated with nilotinib for at least 2 years.

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My cancer has responded very well to nilotinib treatment.

Exclusion Criteria

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

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

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My cancer has a known unusual genetic change.

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I have had a bone marrow or stem cell transplant before.

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I've had medication doses lowered due to low white blood cell or platelet counts in the last 6 months.

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I have tried to stop taking imatinib or nilotinib permanently.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years following nilotinib cessation

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years following nilotinib cessation

This trial's timeline: 3 weeks for screening, Varies for treatment, and 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years following nilotinib cessation for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Percentage of Patients in Treatment Free Remission (TFR) Within 48 Weeks

Secondary study objectives

Change in BCR-ABL (Oncoprotein Product of BCR-ABL Fusion Gene) Transcripts After Re-start of Nilotinib Therapy

Overall Survival (OS)

Percentage of Patients With Stable MMR in Nilotinib Re-initiation Phase

+5 more

Side effects data

From 2019 Phase 3 trial • 846 Patients • NCT00471497

45%

Rash

38%

Headache

32%

Nausea

31%

Alanine aminotransferase increased

24%

Diarrhoea

24%

Nasopharyngitis

24%

Upper respiratory tract infection

23%

Arthralgia

23%

Back pain

22%

Vomiting

22%

Abdominal pain upper

22%

Cough

21%

Alopecia

21%

Thrombocytopenia

20%

Hypertension

20%

Fatigue

20%

Hypophosphataemia

20%

Myalgia

20%

Pruritus

19%

Constipation

19%

Hyperbilirubinaemia

19%

Pain in extremity

18%

Influenza

18%

Pyrexia

17%

Abdominal pain

16%

Anaemia

16%

Oedema peripheral

16%

Aspartate aminotransferase increased

15%

Blood bilirubin increased

14%

Hypercholesterolaemia

14%

Dry skin

14%

Muscle spasms

14%

Lipase increased

14%

Musculoskeletal pain

13%

Dyspepsia

13%

Insomnia

12%

Dizziness

11%

Dyspnoea

11%

Neutropenia

10%

Asthenia

10%

Sinusitis

10%

Oropharyngeal pain

10%

Urinary tract infection

10%

Bone pain

10%

Hyperglycaemia

Non-cardiac chest pain

Leukopenia

Amylase increased

Weight increased

Decreased appetite

Dry eye

Gastroenteritis

Anxiety

Haemorrhoids

Bronchitis

Palpitations

Gastrooesophageal reflux disease

Pharyngitis

Blood alkaline phosphatase increased

Conjunctivitis

Folliculitis

Hyperhidrosis

Erythema

Night sweats

Depression

Gastritis

Flatulence

Blood cholesterol increased

Blood phosphorus decreased

Influenza like illness

Chills

Haemoglobin decreased

Procedural pain

Hyperlipidaemia

Abdominal distension

Hyperuricaemia

Vertigo

Weight decreased

Toothache

Hypoaesthesia

Blood creatinine increased

Coronary artery disease

Angina pectoris

Neck pain

Hypokalaemia

Eczema

Paraesthesia

Face oedema

Herpes zoster

Pneumonia

Transient ischaemic attack

Conjunctival haemorrhage

Myocardial infarction

Acute myocardial infarction

Eyelid oedema

Peripheral arterial occlusive disease

Cellulitis

Pilonidal cyst

Periorbital oedema

Inguinal hernia

Neuropathy peripheral

Azotaemia

Death

Cerebral haemorrhage

Intestinal obstruction

Angina unstable

Migraine

Peripheral artery stenosis

Coronary artery stenosis

Carotid artery stenosis

Renal failure

Benign prostatic hyperplasia

Febrile neutropenia

Gastrointestinal haemorrhage

Myocardial ischaemia

Pancreatitis

Atrial fibrillation

Pancreatitis acute

Hepatic function abnormal

Sepsis

Femur fracture

Road traffic accident

Cerebrovascular accident

Ischaemic stroke

100%

80%

60%

40%

20%

Study treatment Arm

Nilotinib 400 mg BID

Imatinib 400 mg QD

All Patients

Nilotinib 300 mg BID

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: NilotinibExperimental Treatment1 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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

nilotinib

2009

Completed Phase 4

~4370

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

Tyrosine kinase inhibitors (TKIs) like nilotinib target the BCR-ABL fusion protein, a result of the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML). By inhibiting this protein, TKIs prevent the uncontrolled proliferation of leukemic cells. Hypomethylating agents (HMAs) such as azacitidine and decitabine work by reactivating tumor suppressor genes through the inhibition of DNA methylation, thereby slowing the growth of cancer cells. Targeted therapies, including IDH inhibitors and BTK inhibitors, act on specific genetic mutations or pathways involved in leukemia cell survival and proliferation. These treatments are crucial as they offer more precise and effective options, often with fewer side effects compared to traditional chemotherapy, improving the quality of life and outcomes for leukemia patients.

Optimizing the selection of kinase inhibitors for chronic myeloid leukemia patients.