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TKI and Interferon Alpha Evaluation Initiated by the German Chronic Myeloid Leukemia Study Group - the TIGER Study (TIGER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01657604
Recruitment Status : Active, not recruiting
First Posted : August 6, 2012
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. med. Andreas Hochhaus, University of Jena

Brief Summary:
Advances in Chronic Myeloid Leukemia (CML) therapy led to an expected survival prolongation of > 20 years after diagnosis. So far, discontinuation of tyrosine kinase inhibitors led to recurrence of disease in the majority of patients. The trial aims to improve treatment strategies in CML by improving induction therapy and deescalating maintenance therapy using low dose IFN as inducer of immunosurveillance. The trial will provide important data on the duration of active therapy in CML patients. Considering the rapidly increasing prevalence of CML this is of individual but also socioeconomic importance.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: Peginterferon α2b Drug: Nilotinib Phase 3

Detailed Description:

Objectives

Primary:

  • Evaluation of the major molecular response (MMR) rate at 18 months of nilotinib compared to nilotinib+pegylated Interferon alpha (IFN) in adult patients with newly diagnosed Ph/BCR-ABL CML in chronic phase.
  • Evaluation of the feasibility to discontinue drug therapy in stable deep molecular response (MR4) after nilotinib versus IFN maintenance therapy.

Secondary:

  • Evaluation of the efficacy and tolerability of IFN added to nilotinib 2x300 mg/day.
  • Evaluation of the efficacy and tolerability of a maintenance therapy with nilotinib versus IFN after stable MMR after at least 24 months of nilotinib therapy.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 717 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Treatment Optimization of Newly Diagnosed Ph/BCR-ABL Positive Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase With Nilotinib vs. Nilotinib Plus Interferon Alpha Induction and Nilotinib or Interferon Alpha Maintenance Therapy
Actual Study Start Date : August 24, 2012
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Nilotinib+IFN
Patients will receive nilotinib 300 mg BID given as two 150 mg capsules twice daily with Peginterferon α2b at a starting target dose of 30μg/week.
Drug: Peginterferon α2b
Patients will receive nilotinib 300 mg BID given as two 150 mg capsules twice daily with at a starting target dose of 30μg/week. After confirmed MMR or at least 24 mo. after start of therapy, maintenance therapy (nilotinib will be discontinued) will start for a study duration of up to 5 years.
Other Name: Redipen

Active Comparator: Nilotinib
Patients will receive nilotinib 300 mg BID given as two 150 mg capsules twice daily.
Drug: Nilotinib
Patients will receive nilotinib 300 mg BID given as two 150 mg capsules twice daily for a study duration of up to 5 years.
Other Name: Tasigna




Primary Outcome Measures :
  1. MMR rate at 18 months of nilotinib monotherapy versus nilotinib+pegylated interferon alpha [ Time Frame: at least 18 months after start of study treatment ]
    rate of MMR 18 months after randomization for each study treatment

  2. rate of continuous MMR after discontinuation of nilotinib versus pegylated interferon alpha [ Time Frame: at least 12 months after stopping all therapy ]
    rate of patients with molecular relapse (loss of MMR) 12 months after discontinuation of any treatment for CML


Secondary Outcome Measures :
  1. rate of CCyR and MMR [ Time Frame: at 12, 18 and 24 months after start of treatment ]
  2. Time to CCyR, MMR, MR4 and MR4.5 [ Time Frame: date of randomization until time to endpoints or end of study duration (at least 36 months) ]
    this time to-event endpoints give an impression of the velocity of drug response and of the time until a certain remission should be waited for

  3. rate of MR4 and MR4.5 during maintenance therapy and after discontinuation [ Time Frame: start of maintenance therapy (after at least 24 months of treatment) until end of study duration (at least 36 months) ]
  4. Progression-Free Survival (PFS) [ Time Frame: at 12, 24 and 60 months after start of treatment ]
  5. Rate of patients off treatment for at least 6 months [ Time Frame: at 60 months after start of treatment ]
    all patients and comparison of treatment arms

  6. safety and tolerability profile of nilotinib in comparison with nilotinib+pegylated interferon alpha and pegylated interferon alpha [ Time Frame: time of first study treatment until 28 days after stop of study treatment (expected 36 months) ]
    the time of risk is the time while receiving the therapy plus 28 days thereafter

  7. patients compliance to nilotinib based therapies [ Time Frame: until stop of study treatment (at least 36 months) ]
  8. quality of life during induction therapy with ilotinib versus nilotinib+pegylated interferon alpha and during maintenance therapy with nilotinib versus pegylated interferon alpha [ Time Frame: during induction therapy (until at least 24 months), during maintenance therapy (until at least 36 months) ]
  9. pharmacoeconomics of the treatment strategies [ Time Frame: after end of study (expected in December 2020) (up to 8 years) ]
  10. Overall Survival (OS) [ Time Frame: at 12, 24 and 60 months after start of treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Ph chromosome [t(9;22)(q34;q11)]
  • Ph negative cases or patients with variant translocations who are BCR-ABL positive in multiplex PCR (Cross, et al 1994) are eligible as well
  • ECOG performance status of < 2
  • Pretreatment with hydroxyurea for 6 months and imatinib or nilotinib for a duration of up to 6 weeks is permitted
  • Age ≥ 18 years old (no upper age limit given)
  • Normal serum levels ≥ LLN (lower limit of normal) of potassium, magnesium, total calcium corrected for serum albumin, or corrected to within normal limits with supplements
  • ASAT and ALAT ≤ 2.5 x ULN (upper limit of normal) or ≤ 5.0 x ULN if considered due to leukemia
  • Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukemia
  • Total bilirubin ≤ 1.5 x ULN, except known Mb. Gilbert
  • Serum lipase and amylase ≤ 1.5 x ULN
  • Serum creatinine ≤ 2 x ULN
  • Written informed consent prior to any study procedures being performed

Exclusion Criteria:

  • Known impaired cardiac function, including any of the following:

    • Left ventricular ejection fraction (LVEF) < 45%
    • Congenital long QT syndrome
    • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
  • Clinically significant resting bradycardia (< 50 beats per minute)
  • QTc > 450 msec on screening ECG. If QTc > 450 ms and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTc criterion
  • Myocardial infarction within 12 months prior to starting therapy
  • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
  • History of acute (i.e., within 1 year of starting study medication) or chronic pancreatitis
  • Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores > 6), even if controlled
  • Other concurrent uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)
  • Concomitant medications with potential QT prolongation
  • Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Patients who are pregnant or breast feeding, or women of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of nilotinib). Post menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential. Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
  • Active autoimmune disorder, including autoimmune hepatitis
  • Known serious hypersensitivity reactions to peginterferon alfa-2b or interferon alfa-2b or drug excipients
  • Known serious hypersensitivity reactions to nilotinib
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
  • Patients unwilling or unable to comply with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01657604


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Locations
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Czechia
University Hospital and Masaryk University Brno
Brno, Czechia, 62500
Germany
Universitätsklinikum Aachen Medizinische Klinik IV
Aachen, Germany, 52074
Gesundheitszentrum St. Marien GmbH, Onkologie/ Hämatologie Onkologisches Zentrum
Amberg, Germany, 92224
MVZ am Klinikum Arnsberg GmbH, Hämatologie - Internistische Onkologie
Arnsberg, Germany, 56755
Studienzentrum Drs. Klausmann
Aschaffenburg, Germany, 63739
Klinikum Augsburg
Augsburg, Germany, 86156
Klinikum Bayreuth GmbH
Bayreuth, Germany, 95445
Vivantes Netzwerk für Gesundheit GmbH, Klinikum Neukölln, Klinik für Innere Medizin - Hämatologie und Onkologie
Berlin, Germany, 12351
Charité CVK, CC14, Klinik für Hämatologie und Onkologie
Berlin, Germany, 13353
Evangelisches Klinikum Bethel
Bielefeld, Germany, 33611
Universitätsklinikum Bonn Med. Klinik und Poliklinik III, Hämatologie
Bonn, Germany, 53111
Zentrum für Ambulante Hämatologie und Onkologie
Bonn, Germany, 53113
Städtisches Klinikum Braunschweig gGmbh, Medizinische Klinik III - Hämatologie
Braunschweig, Germany, 38114
Klinikum Bremen-Mitte gGmbH
Bremen, Germany, 28177
DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II
Bremen, Germany, 28239
Klinikum Chemnitz gGmbH Klinik für Innere Medizin III
Chemnitz, Germany, 09113
Onkologische Schwerpunktpraxis
Dresden, Germany, 01307
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, Germany, 01307
Onkologisch-Hämatologische Schwerpunktpraxis
Eisenach, Germany, 99817
Dr. med. Ulrich Hauch
Erfurt, Germany, 99084
Onkologische Schwerpunktpraxis Erlangen, Onkologie, Hämatologie
Erlangen, Germany, 91052
Universitätsklinikum Erlangen Medizinische Klinik 5 - Hämatologie und int. Onkologie
Erlangen, Germany, 91054
St.-Antonius-Hospital, Klinik für Hämatologie Onkologie
Eschweiler, Germany, 52249
Klinik für Hämatologie Universitätsklinikum Essen
Essen, Germany, 45122
Klinikum der Goethe Universität
Frankfurt, Germany, 60590
Universitätsklinikum Freiburg Abteilung Innere Medizin I - Hämatologie und Onkologie
Freiburg, Germany, 79106
MVZ-Osthessen GmbH Klinikum Fulda Tumorklinik
Fulda, Germany, 36043
Praxis Dr. med. Schmitt
Gerlingen, Germany, 70839
Dr. med. Hans Werner Tessen, Facharzt für Innere Medizin
Goslar, Germany, 38642
Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere
Greifswald, Germany, 17475
Georg-August Universität Göttingen Abteilung Hämatologie und Onkologie
Göttingen, Germany, 37075
Internistische Gemeinschaftspraxis
Güstrow, Germany, 18273
Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und
Hagen, Germany, 58095
Universitätsklinikum Halle (Saale)
Halle (Saale), Germany, 06120
Gemeinschaftspraxis Hämatologie und internistische
Halle, Germany, 06110
Asklepios Klinik St. Georg, Abteilung Hämatologie, Onkologie, Stammzelltransplantation
Hamburg, Germany, 20099
Universitätsklinikum Hamburg- Eppendorf, Medizinische Klinik 2
Hamburg, Germany, 20246
Evangelisches Krankenhaus Hamm
Hamm, Germany, 59063
St. Barbara-Klinik, Standort St. Josef
Hamm, Germany, 59075
Mediprojekt, Gesellschaft für Medizinstatistik und Projektentwicklung
Hannover, Germany, 30171
Medizinische Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
Hannover, Germany, 30625
Universitätsklinikum Heidelberg Innere Medizin V: Hämatologie, Onkologie und Rheumatologie
Heidelberg, Germany, 69120
Internistische Gemeinschaftspraxis Heilbronn
Heilbronn, Germany, 74072
St. Bernward Krankenhaus Hildesheim
Hildesheim, Germany, 31134
Universitätsklinikum des Saarlandes Klinik für Innere Medizin I
Homburg/ Saar, Germany, 66421
Klinikum Idar-Oberstein GmbH, Innere Medizin I (Hämatologie/Onkologie)
Idar-Oberstein, Germany, 55743
MVZ Onkologie Ingolstadt
Ingolstadt, Germany, 85049
Universitätsklinikum Jena, Klinik für Innere Medizin II, Abt. Hämatologie und internistische Onkologie
Jena, Germany, 07740
Westpfalz-Klinikum GmbH Innere 1
Kaiserslautern, Germany, 67655
Städtisches Klinikum Karlsruhe gGmbH, Medizinische Klinik III: Hämatologie/Onkologie
Karlsruhe, Germany, 76133
St. Vincentius-Kliniken Karlsruhe
Karlsruhe, Germany, 76137
Klinikum Kempten Oberallgäu gGmbH
Kempten, Germany, 87439
Universitätsklinikum Schleswig-Holstein, II. Medizinische Klinik und Poliklinik im Städtischen Krankenhaus Kiel
Kiel, Germany, 24116
InVO, Institut für Versorgungsforschung in der Onkologie
Koblenz, Germany, 56068
Onkologische Gemeinschaftspraxis Dr. M. Neise u. Dr. A. Lollert
Krefeld, Germany, 47805
Onkologische Schwerpunktpraxis
Kronach, Germany, 96317
Universitätsklinikum Köln
Köln, Germany, 50937
Onkologisches Zentrum Gemeinschaftspraxis für Hämato-/ Onkologie, Abt. für Hämato-/ Onkologie im Caritas Krankenhaus
Lebach, Germany, 66822
Onkologisches Schwerpunktpraxis
Leer, Germany, 26789
Universitätsklinikum Leipzig, Department für Innere Medizin
Leipzig, Germany, 04103
Dr. Aldaoud - Dr. Schwarzer Forschungsgesellschaft mbH
Leipzig, Germany, 04289
Krankenhausgesellschaft St. Vincenz mbH Limburg
Limburg An Der Lahn, Germany, 65549
Gemeinschaftspraxis Uhle, Müller, Kröning, Jentsch-Ullrich
Magdeburg, Germany, 39104
Internistische Gemeinschaftspraxis Onkologie/Hämatologie
Mainz, Germany, 55122
Universitätsmedizin der Johannes- Gutenberg Universität Mainz, III. Medizinische Klinik und Poliklinik, Hämatologie, internistische Onkologie und Pneumologie
Mainz, Germany, 55131
Mannheimer Onkologie Praxis
Mannheim, Germany, 68161
Universitätsmedizin Mannheim III. Medizinische Klinik
Mannheim, Germany, 68169
Klinikum der Philipps-Universität Marburg, Klinik für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Immunologie
Marburg, Germany, 35032
Johannes Wesling Klinikum Minden, Mühlenkreikliniken (AöR), Hämatologie/Onkologie
Minden, Germany, 32429
Drs. Schmidt/Schauenberg Onkologie
Muhr am See, Germany, 91735
Stauferklinikum Schwäbisch Gmünd, Zentrum Innere Medizin
Mutlangen, Germany, 73557
Hämatologisch-Onkologische Gemeinschaftspraxis
München, Germany, 80638
Gemeinschaftspraxis Hämatologie/ Onkologie
München, Germany, 81241
MHP Münchener Hämatologie Praxis
München, Germany, 81377
Universitätsklinikum Grosshadern LMU München
München, Germany, 81377
Klinikum rechts der Isar, III. Medizinische Klinik und Poliklinik
München, Germany, 81675
Hämatologisch-Onkologische Schwerpunktpraxis
München, Germany, 81679
Onkologische und hämatologische Schwerpunktpraxis
Neumarkt, Germany, 92318
MVZ I des Klinikums Nürnberg
Nürnberg, Germany, 90419
Klinikum Oldenburg Klinik für Onkologie und Hämatologie / Innere Medizin II
Oldenburg, Germany, 26133
Brüderkrankenhaus St. Josef Paderborn
Paderborn, Germany, 33098
Klinikum Passau, II. Medizinische Klinik
Passau, Germany, 94032
MVZ für Blut- und Krebserkrankungen
Potsdam, Germany, 14467
Klinikum Vest, Behandlungszentrum Recklinghausen, Medizinische Klinik III
Recklinghausen, Germany, 45657
Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie
Regensburg, Germany, 93049
Universitätsklinikum Regensburg Abteilung für Hämatologie und internistische Onkologie
Regensburg, Germany, 93053
Kreiskliniken Reutlingen GmbH, Klinikum am Steinenberg, Medizinische Klinik I
Reutlingen, Germany, 72764
Universitätsmedizin Rostock, ZIM II Klinik für Hämatologie, Onkologie und
Rostock, Germany, 18057
Agaplesion Diakonieklinikum Rotenburg
Rotenburg, Germany, 27356
Leopoldina-Krankenhaus
Schweinfurt, Germany, 97422
Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III: Sektion für Onkologie und Hämatologie
Schwäbisch Hall, Germany, 74523
Klinikverbund Südwest, Kliniken Sindelfingen-Böblingen gGmbH
Sindelfingen, Germany, 71065
Diakonie Klinikum Stuttgart, Medizinische Klinik
Stuttgart, Germany, 70176
Klinikum Mutterhaus der Borromäerinnen
Trier, Germany, 54290
Medizinische Universitätsklinik, Department für Innere Medizin GCP Studienzentrale der Abteilung 2
Tübingen, Germany, 72076
Universitätsklinikum Ulm Klinik für Innere Medizin III
Ulm, Germany, 89081
Medizinisches Versorgungszentrum GmbH
Weiden, Germany, 92637
Dres. med. T. Kamp - R. Eckert Innere/Hämatologie/Onkologie
Wendlingen, Germany, 73240
Rems-Murr-Klinik Winnenden
Winnenden, Germany, 71334
Onkologische Gemeinschaftspraxis Würselen und Stolberg
Würselen, Germany, 52146
Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik II
Würzburg, Germany, 97080
Heinrich-Braun-Klinikum gGmbH
Zwickau, Germany, 08060
Switzerland
Kantonspital Aarau AG
Aarau, Switzerland, 5001
Kantonspital Baden
Baden, Switzerland, 5404
Universitätsspital Basel
Basel, Switzerland, 4031
IOSI; Oncology Institute of Southern Switzerland
Bellinzona, Switzerland, 6500
Inselspital Bern
Bern, Switzerland, 3010
Hopitaux Universitaires de Genève
Geneve, Switzerland, 1211
Département d'oncologie UNIL-CHUV
Lausanne, Switzerland, 1011
Kantonsspital Baselland
Liestal, Switzerland, 4410
Luzerner Kantonsspital
Luzern, Switzerland, 6000
Universitätsspital Zürich
Zürich, Switzerland, 8091
Sponsors and Collaborators
University of Jena
Investigators
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Principal Investigator: Andreas Hochhaus, Prof. MD Jena University Hospital

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Responsible Party: Prof. Dr. med. Andreas Hochhaus, Chair, Dept. Hematology/Oncology, University of Jena
ClinicalTrials.gov Identifier: NCT01657604     History of Changes
Other Study ID Numbers: CML V
2010-024262-22 ( EudraCT Number )
First Posted: August 6, 2012    Key Record Dates
Last Update Posted: April 4, 2019
Last Verified: April 2019

Keywords provided by Prof. Dr. med. Andreas Hochhaus, University of Jena:
CML
Tasigna
Nilotinib
Interferon

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Interferons
Interferon-alpha
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs