A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML.
ENESTPath
A Prospective, Randomized, Open Label, Two Arm Phase III Study to Evaluate Treatment Free Remission (TFR) Rate in Patients With Philadelphia-positive CML After Two Different Durations of Consolidation Treatment With Nilotinib 300mg BID.
2 other identifiers
interventional
620
19 countries
203
Brief Summary
This study aimed to assess the optimal duration of nilotinib 300 mg twice daily (BID) consolidation treatment in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), in order that patients remained in treatment-free remission (≥MR4.0) without molecular relapse 12 months after starting the Treatment-Free Remission (TFR) phase.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2013
Longer than P75 for phase_3
203 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 4, 2012
CompletedFirst Posted
Study publicly available on registry
December 6, 2012
CompletedStudy Start
First participant enrolled
April 15, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 8, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 8, 2020
CompletedResults Posted
Study results publicly available
July 15, 2021
CompletedJuly 15, 2021
June 1, 2021
7.2 years
December 4, 2012
June 23, 2021
June 23, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Who Remained in Treatment Free Remission (TFR) Without Molecular Relapse 12 Months After Entering the TFR Phase
Number of participants who remained in TFR (≥molecular response (MR) 4.0) without molecular relapse 12 months after entering the TFR phase (without re-starting nilotinib therapy) divided by the number of participants who entered the TFR phase and multiplied by 100. Molecular relapse during TFR is defined as the loss of major molecular response (MMR), or the confirmed loss of MR4.0 (defined by 3 consecutive tests less than MR4.0 assessed at 3 consecutive visits during TFR phase). Participants dropping out early from the study during the TFR phase were considered as unsuccessful TFR. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL. MR4.0 is defined as either detectable disease≤0.01% BCR-ABL or undetectable disease in cDNA with≥10,000 ABL transcripts
12 months after entering the TFR phase, which is after 36 months from study treatment start for Nilotinib 24-month treatment arm and after 48 months from study treatment start for Nilotinib 36-month treatment arm
Secondary Outcomes (21)
Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
From baseline up to 24 months after study treatment start
Cumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
From randomization (month 24 after study treatment start) up to 36 months after study treatment start
Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
From baseline up to 24 months after study treatment start
Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
From randomization (month 24 after study treatment start) up to 36 months after study treatment start
Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
From baseline up to 24 months after study treatment start
- +16 more secondary outcomes
Study Arms (3)
Nilotinib 24-month treatment
EXPERIMENTALParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase
Nilotinib 36-month treatment
EXPERIMENTALParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
Not randomized
EXPERIMENTALParticipants were treated with nolotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment.
Interventions
Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.
Eligibility Criteria
You may qualify if:
- Confirmed diagnosis of chronic phase Ph+ CML
- Previous first-line treatment with imatinib for a minimum of 2 years;
- Patient in complete cytogenetic response;
You may not qualify if:
- Previous achievement of MR4.0 at study entry;
- Previous treatment with other target cells inhibitors other than imatinib;
- Patients with any history of detectable atypical Leukemia transcripts or patients with detectable atypical leukemia transcripts at screening;
- Previous anticancer agents for Chronic myeloid leukemia other than imatinib except for cytoreduction;
- 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;
- History of other active malignancies within the 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively;
- Patients who have not recovered from prior surgery;
- Treatment with other investigational agents within 4 weeks of Day 1;
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (208)
Novartis Investigative Site
Linz, Upper Austria, A 4020, Austria
Novartis Investigative Site
Graz, 8036, Austria
Novartis Investigative Site
Linz, 4010, Austria
Novartis Investigative Site
Linz, A-4010, Austria
Novartis Investigative Site
Rankweil, A-6830, Austria
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Salzburg, 5020, Austria
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Brussels, 1070, Belgium
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Liège, 4000, Belgium
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Pleven, 5800, Bulgaria
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Plovdiv, 4002, Bulgaria
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Sofia, 1431, Bulgaria
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Sofia, 1756, Bulgaria
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Varna, 9000, Bulgaria
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Brno-Bohunice, Czech Republic, 625 00, Czechia
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Hradec Králové, CZE, 500 05, Czechia
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Holstebro, DK-7500, Denmark
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Roskilde, 4000, Denmark
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HUS Helsinki, FIN-00029, Finland
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Bayonne, Bayonne Cedex, 64109, France
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Le Mans, Cedex 09, 72037, France
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Paris, Cedex 10, 75475, France
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Caen, Cedex, 14033, France
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Angers, 49033, France
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Bordeaux, 33000, France
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Bordeaux, 33076, France
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Chalon-sur-Saône, 71321, France
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Chambéry, 73011, France
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Clermont-Ferrand, 63003, France
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Corbeil-Essonnes, 91100, France
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Dunkirk, 59240, France
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Grenoble, 38043, France
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La Roche-sur-Yon, 85925, France
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Lille, 59020, France
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Lille, 59037, France
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Lyon, 69373, France
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Marseille, 13273, France
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Metz, 57000, France
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Metz, 57085, France
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Mulhouse, 68070, France
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Nice, 06202, France
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Paris, 75012, France
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Perpignan, 66046, France
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Pontoise, F-95300, France
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Rouen, 76038, France
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Saint-Priest-en-Jarez, 42271, France
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Toulouse, 31059, France
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Mannheim, Baden-Wurttemberg, 68305, Germany
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Augsburg, 86150, Germany
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Bayreuth, 95445, Germany
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Berlin, 13353, Germany
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Braunschweig, 38114, Germany
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Bremen, 28177, Germany
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Chemnitz, 09113, Germany
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Cologne, 50671, Germany
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Dresden, 01307, Germany
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Eisenach, 99817, Germany
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Frankfurt, 60596, Germany
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Georgsmarienhütte, 49124, Germany
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Halle, 06110, Germany
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Hamm, 59063, Germany
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Kiel, 24105, Germany
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Leipzig, 04103, Germany
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Lütten Klein, 18107, Germany
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Magdeburg, 39104, Germany
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Marburg, 35039, Germany
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München, 81241, Germany
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Münster, 48149, Germany
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Nuremberg, 90449, Germany
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Offenburg, 77654, Germany
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Potsdam, 14467, Germany
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Rostock, 18057, Germany
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Rostock, 18059, Germany
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Schorndorf, 73614, Germany
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Schwäbisch Hall, 74523, Germany
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Stuttgart, 70174, Germany
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Velbert, 42551, Germany
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Westerstede, 26655, Germany
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Wiesbaden, 65191, Germany
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Würzburg, 97080, Germany
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Athens, GR, 115 27, Greece
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Thessaloniki, GR, 570 10, Greece
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Athens, 106 76, Greece
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Athens, 115 27, Greece
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Pátrai, 265 00, Greece
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Budapest, 1097, Hungary
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Debrecen, 4032, Hungary
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Szeged, H 6725, Hungary
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Alessandria, AL, 15100, Italy
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Ancona, AN, 60126, Italy
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Avellino, AV, 83100, Italy
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Bari, BA, 70124, Italy
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Bologna, BO, 40138, Italy
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Brescia, BS, 25123, Italy
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Cagliari, CA, 09126, Italy
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Cremona, CR, 26100, Italy
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Catania, CT, 95100, Italy
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Cona, FE, 44100, Italy
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San Giovanni Rotondo, FG, 71013, Italy
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Florence, FI, 50134, Italy
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Genova, GE, 16132, Italy
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Rome, Lazio, 00168, Italy
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Lecce, LE, 73100, Italy
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Livorno, LI, 57124, Italy
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Messina, ME, 98125, Italy
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Milan, MI, 20122, Italy
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Milan, MI, 20132, Italy
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Milan, MI, 20162, Italy
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Modena, MO, 41124, Italy
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Palermo, PA, 90127, Italy
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Palermo, PA, 90146, Italy
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Padua, PD, 35128, Italy
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Pescara, PE, 65124, Italy
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Pisa, PI, 56126, Italy
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Parma, PR, 43100, Italy
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Pavia, PV, 27100, Italy
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Potenza, PZ, 85100, Italy
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Reggio Calabria, RC, 89124, Italy
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Reggio Emilia, RE, 42123, Italy
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Roma, RM, 00133, Italy
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Roma, RM, 00144, Italy
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Roma, RM, 00161, Italy
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Pagani, SA, 84016, Italy
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Siena, SI, 53100, Italy
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Taranto, TA, 74100, Italy
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Orbassano, TO, 10043, Italy
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Torino, TO, 10126, Italy
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Treviso, TV, 31100, Italy
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Udine, UD, 33100, Italy
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Mirano, VE, 30035, Italy
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Venezia, VE, 30174, Italy
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Vicenza, VI, 36100, Italy
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Verona, VR, 37126, Italy
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Napoli, 80131, Italy
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Novara, 28100, Italy
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Perugia, 06129, Italy
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Bergen, NO-5021, Norway
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Oslo, NO-0310, Norway
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Chorzów, 41-500, Poland
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Gdansk, 80 952, Poland
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Katowice, 40-027, Poland
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Krakow, 30-510, Poland
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Olsztyn, 10 561, Poland
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Opole, 45-372, Poland
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Torun, 87 100, Poland
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Warsaw, 02 106, Poland
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Warsaw, 02 776, Poland
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Lisbon, 1099 023, Portugal
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Lisbon, 1749-035, Portugal
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Porto, 4099-001, Portugal
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Porto, 4200 319, Portugal
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Porto, 4200-072, Portugal
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Bucharest, District 2, 022328, Romania
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Bucharest, 030 171, Romania
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Bucharest, 500098, Romania
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Cluj-Napoca, 400124, Romania
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Iași, 700483, Romania
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Sibiu, 550245, Romania
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Timișoara, 300 079, Romania
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Belgrade, 11000, Serbia
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Belgrade, 11070, Serbia
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Niš, 18000, Serbia
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Novi Sad, Serbia
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Bratislava, 85107, Slovakia
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Martin, 03601, Slovakia
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Ljubljana, 1000, Slovenia
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Granada, Andalusia, 18014, Spain
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Jaén, Andalusia, 23007, Spain
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Málaga, Andalusia, 29010, Spain
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Seville, Andalusia, 41009, Spain
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Seville, Andalusia, 41013, Spain
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Palma de Mallorca, Balearic Islands, 07120, Spain
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Sabadell, Barcelona, 08208, Spain
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Donostia / San Sebastian, Basque Country, 20080, Spain
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León, Castille and León, 24071, Spain
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Salamanca, Castille and León, 37007, Spain
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Valladolid, Castille and León, 47011, Spain
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Badalona, Catalonia, 08916, Spain
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Barcelona, Catalonia, 08003, Spain
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Barcelona, Catalonia, 08035, Spain
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Barcelona, Catalonia, 08036, Spain
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Girona, Catalonia, 17007, Spain
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L'Hospitalet de Llobregat, Catalonia, 08907, Spain
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Tarragona, Catalonia, 43005, Spain
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Cáceres, Extremadura, 10003, Spain
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A Coruña, Galicia, 15006, Spain
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Pontevedra, Galicia, 36071, Spain
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Santiago de Compostela, Galicia, 15706, Spain
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Pamplona, Navarre, 31008, Spain
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Alicante, Valencia, 03010, Spain
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Alzira, Valencia, 46600, Spain
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Valencia, Valencia, 46026, Spain
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Granollers, 08402, Spain
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Madrid, 28006, Spain
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Madrid, 28009, Spain
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Madrid, 28031, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Madrid, 28046, Spain
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Madrid, 28222, Spain
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Murcia, 30008, Spain
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Santa Cruz de Tenerife, 38009, Spain
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Zaragoza, 50009, Spain
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Stockholm, SE-171 76, Sweden
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East Yorkshire, HU16 5JQ, United Kingdom
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Edinburgh, EH4 2XU, United Kingdom
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London, EC1A 7BE, United Kingdom
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London, W12 0HS, United Kingdom
Related Publications (1)
Borghi L, Rosti G, Maggi A, Breccia M, Di Bona E, Iurlo A, La Barba G, Sportoletti P, Albano F, Galimberti S, Rivellini F, Cambrin GR, Capodanno I, Cuneo A, Bonifacio M, Sica S, Arcaini L, Capochiani E, Minotto C, Ciceri F, Crugnola M, Di Caprio L, Supekar S, Elena C, Baccarani M, Vegni E. Perspectives and Emotional Experiences of Patients With Chronic Myeloid Leukemia During ENESTPath Clinical Trial and Treatment-Free Remission: Rationale and Protocol of the Italian Substudy. Front Oncol. 2021 May 26;11:638689. doi: 10.3389/fonc.2021.638689. eCollection 2021.
PMID: 34123791DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 4, 2012
First Posted
December 6, 2012
Study Start
April 15, 2013
Primary Completion
July 8, 2020
Study Completion
July 8, 2020
Last Updated
July 15, 2021
Results First Posted
July 15, 2021
Record last verified: 2021-06
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com