Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)

NCT01698905 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CAMN107A24082012-003186-18
• Study Type: interventional
• Target: 163
• Locations: 18 countries
• Sites: 62

Brief Summary

A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at least 3 years and have very small amount of leukemia cells remaining after the nilotinib (Tasigna) treatment will qualify for the study.

Conditions

Chronic Myeloid Leukemia

Keywords

AMN107; CML; Phase II; single arm; open label; nilotinib; treatment-free remission; MR4.5; confirmed loss of MR4; loss of MMR; Ph+ CML-CP

Outcome Measures

Primary Outcomes (1)

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

  TFR is defined as no confirmed loss of MR4 (Molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL \> 0.01% IS. Loss of MMR does not require confirmation. Percentage of patients in TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 48 weeks after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase, and multiplied by 100.

  First 48 weeks following nilotinib cessation.

Secondary Outcomes (8)

• Percentage of Patients in Treatment Free Remission (TFR) Within 96, 144, 192, 264 Weeks and Within 6,7,8,9 and 10 Years

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

• Progression Free Survival (PFS) to Accelerated Phase/Blast Crisis (AP/BC) or Death

  nilotinib cessation up to approximately 580 weeks

• Treatment Free Survival (TFS)

  nilotinib cessation up to approximately 580 weeks

• Overall Survival (OS)

  nilotinib cessation up to approximately 580 weeks

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

  re-start of nilotinib up to approximately 48 weeks

Study Arms (1)

Nilotinib

EXPERIMENTAL

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

Drug: nilotinib

Interventions

nilotinib DRUG

Nilotinib was dosed by weight or body surface area. Nilotinib 300 mg BID or 400 mg BID was be administered orally at approximately 12 hour intervals, and must not have been taken with food. The capsules were to be swallowed whole with water. No food should have been consumed for at least 2 hours before the dose was taken and no additional food should have been consumed for at least one hour after the dose was taken. Patients were also allowed to enter this study on the same dose they were taking prior to study entry. Patients who required permanent dose reduction from their original starting dose were to be allowed to enter this study on the same dose only if the patient maintained this dose for a minimum of 6 months prior to study entry.

Also known as: AMN107

Nilotinib

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients \>= 18 years of age
• ECOG Performance Status of 0, 1, or 2
• Patient with diagnosis of BCR-ABL positive CML CP
• Patient has received a minimum of 3 years of tyrosine kinase inhibitor treatment (first with imatinib (\> 4 weeks) and then switched to nilotinib) since initial diagnosis
• Patient has at least 2 years of nilotinib treatment prior to study entry.
• Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
• Adequate end organ function as defined by:
• Direct bilirubin ≤ 1.5 x ULN except for i) patient with documented Gilbert's syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range)
• SGOT(AST) and SGPT(ALT) \< 3 x ULN (upper limit of normal)
• Serum lipase ≤ 2 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• Serum creatinine \< 1.5 x ULN
• Patients must have the following electrolyte values ≥ LLN (lower limit of normal) limits or corrected to within normal limits with supplements prior to the first dose of study medication:
• Potassium
• Magnesium

You may not qualify if:

• Prior AP, BC or allo-transplant
• Patient has documented MR4.5 at the time when switched from imatinib to nilotinib
• Patients with known atypical transcript
• CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past)
• Dose reductions due to neutropenia or thrombocytopenia in the past 6 months
• Patient ever attempted to permanently discontinue imatinib or nilotinib treatment
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (62)

USC Kenneth Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Indiana Blood and Marrow Institute

Beech Grove, Indiana, 46107, United States

Location

St Agnes Hospital

Baltimore, Maryland, 21229, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0144, United States

Location

Compass Oncology

Vancouver, Washington, 98683, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1221ADC, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1114AAN, Argentina

Location

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

Location

Novartis Investigative Site

Box Hill, Victoria, 3128, Australia

Location

Novartis Investigative Site

Antwerp, 2060, Belgium

Location

Novartis Investigative Site

Goiânia, Goiás, 74605-050, Brazil

Location

Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20211-030, Brazil

Location

Novartis Investigative Site

Rio de Janiero, Rio de Janeiro, 20231-050, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

Novartis Investigative Site

Campinas, São Paulo, 13083-970, Brazil

Location

Novartis Investigative Site

Hamilton, Ontario, L8V 5C2, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H1T 2M4, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1J 1Z4, Canada

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Grenoble, 38043, France

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Strasbourg, 67085, France

Location

Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

Location

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68305, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Heilbronn, 74072, Germany

Location

Novartis Investigative Site

Potsdam, 14467, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Athens, Attica, 106 76, Greece

Location

Novartis Investigative Site

Larissa, GR, 411 10, Greece

Location

Novartis Investigative Site

Athens, 18547, Greece

Location

Novartis Investigative Site

Haifa, 3109601, Israel

Location

Novartis Investigative Site

Petah Tikva, 4941492, Israel

Location

Novartis Investigative Site

Ramat Gan, 5265601, Israel

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 464 8681, Japan

Location

Novartis Investigative Site

Narita, Chiba, 286-8523, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Novartis Investigative Site

Kurume, Fukuoka, 830-0011, Japan

Location

Novartis Investigative Site

Akita, 010-8543, Japan

Location

Novartis Investigative Site

Aomori, 030 8553, Japan

Location

Novartis Investigative Site

Chiba, 2608677, Japan

Location

Novartis Investigative Site

Monterrey, Nuevo León, 64718, Mexico

Location

Novartis Investigative Site

Krakow, Lesser Poland Voivodeship, 30-727, Poland

Location

Novartis Investigative Site

Gdansk, 80-952, Poland

Location

Novartis Investigative Site

Warsaw, 00-791, Poland

Location

Novartis Investigative Site

Moscow, 125167, Russia

Location

Novartis Investigative Site

Saint Petersburg, 191024, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197341, Russia

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Santander, Cantabria, 39008, Spain

Location

Novartis Investigative Site

Badalona, Catalonia, 08916, Spain

Location

Novartis Investigative Site

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Novartis Investigative Site

Alicante, 03010, Spain

Location

Novartis Investigative Site

Madrid, 28006, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Liverpool, L7 8XP, United Kingdom

Location

Novartis Investigative Site

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• Mahon FX, Boquimpani C, Kim DW, Benyamini N, Clementino NCD, Shuvaev V, Ailawadhi S, Lipton JH, Turkina AG, De Paz R, Moiraghi B, Nicolini FE, Dengler J, Sacha T, Takahashi N, Fellague-Chebra R, Acharya S, Wong S, Jin Y, Hughes TP. Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study. Ann Intern Med. 2018 Apr 3;168(7):461-470. doi: 10.7326/M17-1094. Epub 2018 Feb 20.

  PMID: 29459949 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2012
• First Posted: October 3, 2012
• Study Start: December 20, 2012
• Primary Completion: November 26, 2015
• Study Completion: January 29, 2025
• Last Updated: September 2, 2025
• Results First Posted: January 13, 2021

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

IL (3); CA (4); FR (5); DE (5); AR (2); JP (7); RU (3); GB (2); GR (3); US (5); KR (1); BR (6); SG (1); BE (1); ME (1); PL (3); AU (2); ES (8)