Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients

NCT01784068 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CAMN107I22012012-004092-40
• Study Type: interventional
• Target: 215
• Locations: 19 countries
• Sites: 113

Brief Summary

The main purpose of the study was to investigate whether nilotinib treatment can be safely suspended with no recurrence of CML in selected patients who responded optimally on this treatment

Conditions

Chronic Myelogenous Leukemia

Keywords

AMN107; Ph+ CML-CP; chronic phase; nilotinib treatment; 2 years treatment; MR 4.5; Loss of MR 4; Loss of MMR; CML

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Who Are in MMR (Major Molecular Response) at 48 Weeks After Starting the Treatment-free Remission (TFR) Phase

  Primary endpoint was the percentage of participants who were in MMR at 48 weeks after starting the TFR phase and is calculated by dividing the number of patients with MMR at 48 weeks after starting the TFR phase with no loss of MMR and no re-initiation of nilotinib therapy in the first 48 weeks after starting the TFR phase by the number of patients who entered the TFR phase. Patients who required re-initiation of treatment were considered as non-responders.

  48 weeks

Secondary Outcomes (15)

• Percentage of Patients Who Are in MR4.5 (BCR-ABL ≤ 0.0032% IS) at 48 Weeks After Starting the TFR Phase

  48 weeks

• Percentage of Patients Who Are in MMR at 96, 144,192, 264 Weeks and at the End of 6, 7, 8, 9 and 10 Years After Starting the TFR Phase

  96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years

• Percentage of Patients Who Are in MR4.5 at 96, 144, 192, 264 Weeks and at the End of 6, 7, 8, 9 and 10 Years After Starting the TFR Phase

  96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years

• Percentage of Patients in MMR at 48, 96, 144, 192, 264 Weeks and at the End of 6, 7, 8, 9 and 10 Years After Starting the TFR Phase of Nilotinib

  48, 96, 144, 192, 264 weeks and at the end of 6, 7, 8, 9 and 10 years

• Percentage of Patients in MR4.5 at 48, 96, 144, 192, 264 Weeks and at the End of 6, 7, 8, 9 and 10 Years After Starting the TFR Phase of Nilotinib

  48, 96, 144, 192, 264 weeks, end of 6, 7, 8, 9 and 10 years

Study Arms (1)

Nilotinib followed by treatment-free

EXPERIMENTAL

Patients who received a minimum of 2 years of first line nilotinib treatment and with pre-screen PCR results in ≥ MR4.5 entered the consolidation phase of the study (52 weeks - nilotinib 300 mg BID). Patients with Minimal Residual Disease (MRD) at the end of this phase entered the Treatment-Free Remission (TFR) phase where no treatment was given. Non eligible patients will enter the continuation phase of the study. Patients with MRD at the end of the continuation phase will enter the TFR-2 phase of the study where no treatment is given. Non eligible patients will enter the prolonged continuation phase of the study. If at any time during TFR or TFR-2 the patient loses MMR, nilotinib treatment will be immediately re-initiated (nilotinib 300 mg BID).

Drug: Nilotinib followed by treatment-free

Interventions

Nilotinib followed by treatment-free DRUG

Nilotinib is being used as commercial available capsules (except in Japan where clinical supplies is used) of 150 mg and 200 mg strength. Treatment occurs during consolidation, continuation, prolonged continuation, re-initiation and re-initiation-2 phases of the study.

Also known as: AMN107

Nilotinib followed by treatment-free

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
• Minimum of 2 calendar years of nilotinib treatment with at least the last 12 months of nilotinib treatment prior to pre-screening at approved total daily dose of 600 mg BID or at a reduced dose of 400 mg QD if required from the perspective of tolerance for BCR-ABL positive CML in documented chronic phase at the time of diagnosis
• Evidence of typical BCR-ABL transcripts (b3a2 and/or b2a2) at the time of CML-CP diagnosis i.e. prior to first start of TKI treatment which are amenable to standardized RT-PCR quantification"
• Patient in MR4.5 at prescreening at Novartis designated lab
• ECOG performance status of 0-2
• Adequate end organ function as defined by:
• Direct bilirubin ≤ 1.5 x ULN except for i) patients 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 i.e. equivalent to ≤ Grade 1 NCI-CTCAE v.4.03
• Serum lipase ≤ 2 x ULN i.e. equivalent to ≤ Grade 2 NCI-CTCAE v.4.03
• Alkaline phosphatase ≤ 2.5 x ULN
• Serum creatinine \< 1.5 x ULN
• Patients must have the following electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:
• Potassium (suggested keep to prevent issues with QT and/or rhythm abnormalities)
• Magnesium (suggested keep to prevent issues with QT and/or rhythm abnormalities)
• Total calcium (corrected for serum albumin)

You may not qualify if:

• Previous treatment with BCR-ABL inhibitors other than nilotinib for more than a total cumulative duration of 4 weeks
• Previous treatment with alpha-interferon of any duration
• Previous anticancer agents for CML other than nilotinib except for cytoreduction after CML diagnosis until up to 4 weeks after first dose of nilotinib
• Known second chronic phase of CML after previous progression to AP/BC
• Poorly controlled diabetes mellitus (defined as HbA1c \> 9%)
• Impaired cardiac function including any one of the following:
• LVEF \< 45% or below the institutional lower limit of the normal range (whichever is higher)
• Inability to determine the QT interval on ECG, except for patients with evidence of measurable QT interval at the time of CML diagnosis (e.g. prior to first start of TKI treatment) and who have no documented clinical signs of cardiovascular disease and/or clinical signs of conduction abnormality.
• Complete left bundle branch block
• Right bundle branch block plus left anterior or posterior hemiblock
• Use of a ventricular-paced pacemaker
• Congenital 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
• History or clinical signs of myocardial infarction within 1 year of study entry

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (113)

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Lakes Research

Miami Lakes, Florida, 33014, United States

Location

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214-3728, United States

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Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering

New York, New York, 10017, United States

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Oregon Health Sciences University

Portland, Oregon, 97239, United States

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Cancer Centers of the Carolinas

Greenville, South Carolina, 29605, United States

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Tennessee Oncology PLLC

Chattanooga, Tennessee, 37404, United States

Location

Community Cancer Trials of Utah

Ogden, Utah, 84405, United States

Location

Novartis Investigative Site

Buenos Aires, C1114AAN, Argentina

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Novartis Investigative Site

Graz, 8036, Austria

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Novartis Investigative Site

Rankweil, A-6830, Austria

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Novartis Investigative Site

Salzburg, 5020, Austria

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Novartis Investigative Site

Vienna, 1140, Austria

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Novartis Investigative Site

Vienna, A-1130, Austria

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Novartis Investigative Site

Sint-Niklaas, Oost Vlaanderen, 9100, Belgium

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Novartis Investigative Site

Brussels, 1090, Belgium

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Brussels, 1200, Belgium

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Charleroi, 6000, Belgium

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Ghent, 9000, Belgium

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Novartis Investigative Site

Kortrijk, 8500, Belgium

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Liège, 4000, Belgium

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Novartis Investigative Site

Varna, 9000, Bulgaria

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Bogota, Cundinamarca, 111411, Colombia

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Montería, 230004, Colombia

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Aarhus N, 8200, Denmark

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Bayonne, Bayonne Cedex, 64109, France

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Saint Priest En Jarez, Pays de la Loire Region, 42270, France

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Bordeaux, 33076, France

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Brest, 29609, 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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Nantes, 44093, France

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Rouen, 76038, France

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Strasbourg, 67000, France

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Strasbourg, 67085, France

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Toulouse, 31059, France

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Mannheim, Baden-Wurttemberg, 68305, Germany

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Frankfurt am Main, Hesse, 60590, Germany

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Düsseldorf, North Rhine-Westphalia, 40225, Germany

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Leipzig, Saxony, 04103, Germany

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Lübeck, Schleswig-Holstein, 23563, Germany

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Jena, Thuringia, 07740, Germany

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Aachen, 52074, Germany

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Bayreuth, 95445, Germany

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Berlin, 13353, Germany

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Bonn, 53105, Germany

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Bottrop, 46236, Germany

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Dresden, 01307, Germany

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Düsseldorf, 40479, Germany

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Goslar, 38642, Germany

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Hamburg, 20246, Germany

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Hamburg, 22417, Germany

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Magdeburg, 39104, Germany

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Mainz, 55131, Germany

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Stuttgart, 70376, Germany

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Ulm, 89081, Germany

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Athens, 106 76, Greece

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Athens, 115 27, Greece

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Budapest, H-1083, Hungary

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Szeged, 6720, Hungary

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Dublin, D03 VX82, Ireland

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Galway, 12074, Ireland

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Ancona, AN, 60126, Italy

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Brescia, BS, 25123, Italy

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Cona, FE, 44100, Italy

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Florence, FI, 50134, Italy

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Genova, GE, 16132, Italy

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Nuoro, NU, 08100, Italy

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Perugia, PG, 06129, Italy

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Reggio Calabria, RC, 89100, Italy

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Roma, RM, 00161, Italy

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Orbassano, TO, 10043, Italy

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Terni, TR, 05100, Italy

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Napoli, 80132, Italy

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Novara, 28100, Italy

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Kashiwa, Chiba, 277-8567, Japan

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Sapporo, Hokkaido, 060 8648, Japan

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Sagamihara, Kanagawa, 252-0375, Japan

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Ōsaka-sayama, Osaka, 589 8511, Japan

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Suita, Osaka, 565 0871, Japan

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Saga, Saga-ken, 849-8501, Japan

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Kawagoe, Saitama, 350 8550, Japan

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Shimotsuga Gun, Tochigi, 321-0293, Japan

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Bunkyo-ku, Tokyo, 113-8519, Japan

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Shinjuku Ku, Tokyo, 160-0023, Japan

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Akita, 010-8543, Japan

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Kumamoto, 860-8556, Japan

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Groningen, 9713 GZ, Netherlands

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Gdansk, 80-952, Poland

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Warsaw, 02 106, Poland

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Terrassa, Catalonia, 08221, Spain

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Ourense, Galicia, 32005, Spain

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Pamplona, Navarre, 31008, Spain

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Oviedo, Principality of Asturias, 33011, Spain

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

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Barakaldo, Vizcaya, 48903, Spain

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Barcelona, 08041, Spain

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Las Palmas de Gran Canaria, 35010, Spain

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Novartis Investigative Site

Madrid, 28006, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Madrid, 28040, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Madrid, 28046, Spain

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Tarragona, 43005, Spain

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Novartis Investigative Site

Lund, SE-221 85, Sweden

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Stockholm, SE-171 76, Sweden

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Uppsala, SE-751 85, Sweden

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Cardiff, CF14 4XW, United Kingdom

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Oxford, OX3 7LE, United Kingdom

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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 Pharmaceuticals

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: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: February 5, 2013
• Study Start: March 19, 2013
• Primary Completion: May 31, 2016
• Study Completion: January 23, 2025
• Last Updated: September 10, 2025
• Results First Posted: January 14, 2021

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (10); IE (2); GB (2); AR (1); BE (7); CO (2); HU (2); NL (1); ES (14); SE (3); IT (13); DK (1); DE (21); PL (2); BU (1); AU (5); JP (12); FR (12); GR (2)