Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients (ENESTxtnd)

Extending Molecular Responses With Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients in Chronic Phase

This study will further investigate the safety and efficacy of nilotinib in newly diagnosed chronic myeloid leukemia patients in the chronic phase

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukemia
• Intervention / Treatment: Drug: Nilotinib

• Study Type: Interventional
• Enrollment (Actual): 421
• Phase: Phase 3

Contacts and Locations

Study Locations

• Algeria
  • Oran, Algeria, 31000
    • Novartis Investigative Site
  • Bouzareah
    • Alger, Bouzareah, Algeria, 16000
      • Novartis Investigative Site
• Argentina
  • Buenos Aires, Argentina, C1114AAN
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1221ADC
      • Novartis Investigative Site
  • Entre Rios
    • Paraná, Entre Rios, Argentina, E3100BBJ
      • Novartis Investigative Site
• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2605
      • Novartis Investigative Site
  • New South Wales
    • Concord NSW, New South Wales, Australia, 2139
      • Novartis Investigative Site
    • Gosford, New South Wales, Australia, 2250
      • Novartis Investigative Site
    • Kingswood, New South Wales, Australia, 2747
      • Novartis Investigative Site
    • Kogarah, New South Wales, Australia, 2217
      • Novartis Investigative Site
    • Liverpool, New South Wales, Australia, 2170
      • Novartis Investigative Site
    • St. Leonards, New South Wales, Australia, 2065
      • Novartis Investigative Site
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • Queensland
    • Douglas, Queensland, Australia, 4810
      • Novartis Investigative Site
    • Woolloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
    • Bedford Park, South Australia, Australia, 5042
      • Novartis Investigative Site
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Novartis Investigative Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Novartis Investigative Site
    • Clayton, Victoria, Australia, 3168
      • Novartis Investigative Site
    • Fitzroy, Victoria, Australia, 3065
      • Novartis Investigative Site
    • Heidelberg, Victoria, Australia, 3084
      • Novartis Investigative Site
    • Parkville, Victoria, Australia, 3050
      • Novartis Investigative Site
    • Wodonga, Victoria, Australia, 3690
      • Novartis Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
    • Perth, Western Australia, Australia, 6000
      • Novartis Investigative Site
• Brazil
  • BA
    • Salvador, BA, Brazil, 41253-190
      • Novartis Investigative Site
  • GO
    • Goiania, GO, Brazil, 74605-020
      • Novartis Investigative Site
  • PR
    • Curitiba, PR, Brazil, 81520-060
      • Novartis Investigative Site
  • RS
    • Porto Alegre, RS, Brazil, 90430-091
      • Novartis Investigative Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Novartis Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Novartis Investigative Site
    • Vancouver, British Columbia, Canada, V6Z1Y6
      • Novartis Investigative Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Novartis Investigative Site
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Novartis Investigative Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Novartis Investigative Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Novartis Investigative Site
    • Brampton, Ontario, Canada, L6R 3J7
      • Novartis Investigative Site
    • Hamilton, Ontario, Canada, L8V 5C2
      • Novartis Investigative Site
    • London, Ontario, Canada, N6A 4G5
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
    • Weston, Ontario, Canada, M9N 1N8
      • Novartis Investigative Site
    • Windsor, Ontario, Canada, N8W 2X3
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Novartis Investigative Site
    • Québec, Quebec, Canada, G1J 1Z4
      • Novartis Investigative Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Novartis Investigative Site
• Egypt
  • Alexandria, Egypt, 21131
    • Novartis Investigative Site
  • Cairo, Egypt
    • Novartis Investigative Site
  • Cairo, Egypt, 11566
    • Novartis Investigative Site
  • Mansoura, Egypt, 35516
    • Novartis Investigative Site
• India
  • Chennai
    • Tamil Nadu, Chennai, India, 600035
      • Novartis Investigative Site
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Novartis Investigative Site
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Petach Tikva, Israel, 49100
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5266202
    • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon, 166830
    • Novartis Investigative Site
  • Saida, Lebanon, 652
    • Novartis Investigative Site
• Malaysia
  • Pulau Pinang, Malaysia, 10990
    • Novartis Investigative Site
  • Selangor, Malaysia, 68000
    • Novartis Investigative Site
• Mexico
  • San Luis Potosi, Mexico, 78416
    • Novartis Investigative Site
  • Sonora
    • Hermosillo, Sonora, Mexico, 83000
      • Novartis Investigative Site
• Oman
  • Muscat, Oman, 123
    • Novartis Investigative Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620137
    • Novartis Investigative Site
  • Irkutsk, Russian Federation, 664079
    • Novartis Investigative Site
  • Moscow, Russian Federation, 125167
    • Novartis Investigative Site
  • Moscow, Russian Federation, 125284
    • Novartis Investigative Site
  • Nizhnii Novgorod, Russian Federation, 603126
    • Novartis Investigative Site
  • Rostov-on-Don, Russian Federation, 344090
    • Novartis Investigative Site
  • Rostov-on-Don, Russian Federation, 344022
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 191024
    • Novartis Investigative Site
  • St-Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • Tula, Russian Federation, 300053
    • Novartis Investigative Site
  • Russia
    • Arkhangelsk, Russia, Russian Federation, 163045
      • Novartis Investigative Site
    • Novosibirsk, Russia, Russian Federation, 630051
      • Novartis Investigative Site
    • Perm, Russia, Russian Federation, 614077
      • Novartis Investigative Site
    • Ryazan, Russia, Russian Federation, 390039
      • Novartis Investigative Site
    • St Petersburg, Russia, Russian Federation, 197341
      • Novartis Investigative Site
    • Tumen, Russia, Russian Federation, 625023
      • Novartis Investigative Site
• Saudi Arabia
  • Dammam, Saudi Arabia, 15215
    • Novartis Investigative Site
  • Jeddah, Saudi Arabia, 21423
    • Novartis Investigative Site
  • Jeddah, Saudi Arabia, 21499
    • Novartis Investigative Site
  • Riyadh, Saudi Arabia, 11211
    • Novartis Investigative Site
  • Riyadh, Saudi Arabia, 11426
    • Novartis Investigative Site
• South Africa
  • Bloemfontein, South Africa, 9301
    • Novartis Investigative Site
  • Observatory, South Africa, 7925
    • Novartis Investigative Site
  • Parktown, South Africa, 2193
    • Novartis Investigative Site
  • Pretoria, South Africa, 0002
    • Novartis Investigative Site
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Novartis Investigative Site
• Taiwan
  • Lin-Kou, Taiwan, 33305
    • Novartis Investigative Site
  • Niaosong Township, Taiwan, 83301
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taiwan, ROC
    • Taipei, Taiwan, ROC, Taiwan, 112
      • Novartis Investigative Site
• Thailand
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
  • Muang, Thailand, 40002
    • Novartis Investigative Site
• Tunisia
  • Tunis, Tunisia, 1008
    • Novartis Investigative Site
  • Tunisie
    • Sousse, Tunisie, Tunisia, 4000
      • Novartis Investigative Site
• United Arab Emirates
  • Dubai, United Arab Emirates
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-Patients with chronic myeloid leukemia in the chronic phase diagnosed within 6 months of study entry

Exclusion Criteria:

• Treatment with tyrosine kinase inhibitor or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with exception of hydroxyurea and/or anagrelide
• Uncontrolled congestive heart failure or hypertension
• Myocardial infarction or unstable angina pectoris within past 12 months
• Known T315I mutations
• QTcF >450 msec
• Significant arrhythmias

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nilotinib; 300 mg BID

Drug: Nilotinib; This was an open-label, single-arm, prospective, multi-center, Phase IIIb clinical study with nilotinib 300 mg bid treatment in newly diagnosed CML-CP patients not previously treated with imatinib therapy and diagnosed within 6 months of study entry. For patients insufficiently responding to nilotinib 300 mg bid, the dose may have been increased to 400 mg bid. Among patients with adverse events who had dose reduction, this study also allowed a possible re-escalation to 300 mg bid.; Other Names: AMN107

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients Achieving MMR by 12 Months	MMR is defined as BCR-ABL ratio (%) on IS <= 0.1% (corresponds to >=3 log reduction of BCR-ABL transcripts from standardized baseline value). Clopper-Pearson method	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Molecular Response at 24 Months	Estimated median time to first MMR by Kaplan-Meier method	24 months
Duration of Major Molecular Response	Kaplan-Meier estimates of duration of first MMR among patients who achieved MMR (FAS) Duration of first MMR (months) = (Minimum date of (loss of first MMR , CML-related death, progression to AP/BC during study treatment, censoring) - date of first MMR + 1) / 30.4375	3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detected
Complete Cytogenetic Response	Complete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.	6 months
Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation.	* CCyR = 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics. Duration of first CCyR (months) = (date of CCyR loss or censoring - date of first CCyR +1) / 30.4375	6,12,18 and 24 months
Overall Survival	OS was defined as the time between date of study entry and date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.	3, 6, 9, 12, 15, 18, 21, 24 Months
Kaplan-Meier Estimates of Progression-free Survival	PFS was defined as the time from the date of study entry to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring on treatment.	3,6,9,12,15,18,21,and 24 months
Kaplan-Meier Estimates of Failure-free Survival	Time to event (months) = (date of event or censoring - date of study entry + 1) / 30.4375. Date of event is the earliest date of the following events during treatment : discontinuation of nilotinib for nilotinib-related adverse events, death due to any cause, progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR. Time is censored at the date of last assessment in the trial for patients without event.	3,6,9,12,15,18,21,and 24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, Quach H, Pavlovsky C, Louw VJ, Shih LY, Turkina AG, Meillon L, Jin Y, Acharya S, Dalal D, Lipton JH. Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd. Br J Haematol. 2017 Oct;179(2):219-228. doi: 10.1111/bjh.14829. Epub 2017 Jul 12.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: December 2, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Estimate): March 3, 2016
• Last Update Submitted That Met QC Criteria: February 3, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Philadelphia chromosome; nilotinib,; Chronic myeloid leukemia,; CML,; myelogenous,
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: CAMN107E2401