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

NCT ID: NCT01657604

Last Updated: 2023-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 717 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-24
• Study Completion Date: 2022-05-31

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.

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.

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Peginterferon α2b

Intervention Type: DRUG

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.

Nilotinib

Patients will receive nilotinib 300 mg BID given as two 150 mg capsules twice daily.

Group Type: ACTIVE_COMPARATOR

Nilotinib

Intervention Type: DRUG

Patients will receive nilotinib 300 mg BID given as two 150 mg capsules twice daily for a study duration of up to 5 years.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Redipen; Tasigna

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Jena

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. med. Andreas Hochhaus

Chair, Dept. Hematology/Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andreas Hochhaus, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Jena University Hospital

Locations

University Hospital and Masaryk University Brno

Brno, , Czechia

Universitätsklinikum Aachen Medizinische Klinik IV

Aachen, , Germany

Gesundheitszentrum St. Marien GmbH, Onkologie/ Hämatologie Onkologisches Zentrum

Amberg, , Germany

MVZ am Klinikum Arnsberg GmbH, Hämatologie - Internistische Onkologie

Arnsberg, , Germany

Studienzentrum Drs. Klausmann

Aschaffenburg, , Germany

Klinikum Augsburg

Augsburg, , Germany

Klinikum Bayreuth GmbH

Bayreuth, , Germany

Vivantes Netzwerk für Gesundheit GmbH, Klinikum Neukölln, Klinik für Innere Medizin - Hämatologie und Onkologie

Berlin, , Germany

Charité CVK, CC14, Klinik für Hämatologie und Onkologie

Berlin, , Germany

Evangelisches Klinikum Bethel

Bielefeld, , Germany

Universitätsklinikum Bonn Med. Klinik und Poliklinik III, Hämatologie

Bonn, , Germany

Zentrum für Ambulante Hämatologie und Onkologie

Bonn, , Germany

Städtisches Klinikum Braunschweig gGmbh, Medizinische Klinik III - Hämatologie

Braunschweig, , Germany

Klinikum Bremen-Mitte gGmbH

Bremen, , Germany

DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II

Bremen, , Germany

Klinikum Chemnitz gGmbH Klinik für Innere Medizin III

Chemnitz, , Germany

Universitätsklinikum Köln

Cologne, , Germany

Onkologische Schwerpunktpraxis

Dresden, , Germany

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, , Germany

Onkologisch-Hämatologische Schwerpunktpraxis

Eisenach, , Germany

Dr. med. Ulrich Hauch

Erfurt, , Germany

Onkologische Schwerpunktpraxis Erlangen, Onkologie, Hämatologie

Erlangen, , Germany

Universitätsklinikum Erlangen Medizinische Klinik 5 - Hämatologie und int. Onkologie

Erlangen, , Germany

St.-Antonius-Hospital, Klinik für Hämatologie Onkologie

Eschweiler, , Germany

Klinik für Hämatologie Universitätsklinikum Essen

Essen, , Germany

Klinikum der Goethe Universität

Frankfurt, , Germany

Universitätsklinikum Freiburg Abteilung Innere Medizin I - Hämatologie und Onkologie

Freiburg im Breisgau, , Germany

MVZ-Osthessen GmbH Klinikum Fulda Tumorklinik

Fulda, , Germany

Praxis Dr. med. Schmitt

Gerlingen, , Germany

Dr. med. Hans Werner Tessen, Facharzt für Innere Medizin

Goslar, , Germany

Georg-August Universität Göttingen Abteilung Hämatologie und Onkologie

Göttingen, , Germany

Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere

Greifswald, , Germany

Internistische Gemeinschaftspraxis

Güstrow, , Germany

Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und

Hagen, , Germany

Gemeinschaftspraxis Hämatologie und internistische

Halle, , Germany

Universitätsklinikum Halle (Saale)

Halle, , Germany

Asklepios Klinik St. Georg, Abteilung Hämatologie, Onkologie, Stammzelltransplantation

Hamburg, , Germany

Universitätsklinikum Hamburg- Eppendorf, Medizinische Klinik 2

Hamburg, , Germany

Evangelisches Krankenhaus Hamm

Hamm, , Germany

St. Barbara-Klinik, Standort St. Josef

Hamm, , Germany

Mediprojekt, Gesellschaft für Medizinstatistik und Projektentwicklung

Hanover, , Germany

Medizinische Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation

Hanover, , Germany

Universitätsklinikum Heidelberg Innere Medizin V: Hämatologie, Onkologie und Rheumatologie

Heidelberg, , Germany

Internistische Gemeinschaftspraxis Heilbronn

Heilbronn, , Germany

St. Bernward Krankenhaus Hildesheim

Hildesheim, , Germany

Universitätsklinikum des Saarlandes Klinik für Innere Medizin I

Homburg/ Saar, , Germany

Klinikum Idar-Oberstein GmbH, Innere Medizin I (Hämatologie/Onkologie)

Idar-Oberstein, , Germany

MVZ Onkologie Ingolstadt

Ingolstadt, , Germany

Universitätsklinikum Jena, Klinik für Innere Medizin II, Abt. Hämatologie und internistische Onkologie

Jena, , Germany

Westpfalz-Klinikum GmbH Innere 1

Kaiserslautern, , Germany

Städtisches Klinikum Karlsruhe gGmbH, Medizinische Klinik III: Hämatologie/Onkologie

Karlsruhe, , Germany

St. Vincentius-Kliniken Karlsruhe

Karlsruhe, , Germany

Klinikum Kempten Oberallgäu gGmbH

Kempten, , Germany

Universitätsklinikum Schleswig-Holstein, II. Medizinische Klinik und Poliklinik im Städtischen Krankenhaus Kiel

Kiel, , Germany

InVO, Institut für Versorgungsforschung in der Onkologie

Koblenz, , Germany

Onkologische Gemeinschaftspraxis Dr. M. Neise u. Dr. A. Lollert

Krefeld, , Germany

Onkologische Schwerpunktpraxis

Kronach, , Germany

Onkologisches Zentrum Gemeinschaftspraxis für Hämato-/ Onkologie, Abt. für Hämato-/ Onkologie im Caritas Krankenhaus

Lebach, , Germany

Onkologisches Schwerpunktpraxis

Leer, , Germany

Universitätsklinikum Leipzig, Department für Innere Medizin

Leipzig, , Germany

Dr. Aldaoud - Dr. Schwarzer Forschungsgesellschaft mbH

Leipzig, , Germany

Krankenhausgesellschaft St. Vincenz mbH Limburg

Limburg an der Lahn, , Germany

Gemeinschaftspraxis Uhle, Müller, Kröning, Jentsch-Ullrich

Magdeburg, , Germany

Internistische Gemeinschaftspraxis Onkologie/Hämatologie

Mainz, , Germany

Universitätsmedizin der Johannes- Gutenberg Universität Mainz, III. Medizinische Klinik und Poliklinik, Hämatologie, internistische Onkologie und Pneumologie

Mainz, , Germany

Mannheimer Onkologie Praxis

Mannheim, , Germany

Universitätsmedizin Mannheim III. Medizinische Klinik

Mannheim, , Germany

Klinikum der Philipps-Universität Marburg, Klinik für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Immunologie

Marburg, , Germany

Johannes Wesling Klinikum Minden, Mühlenkreikliniken (AöR), Hämatologie/Onkologie

Minden, , Germany

Drs. Schmidt/Schauenberg Onkologie

Muhr am See, , Germany

Stauferklinikum Schwäbisch Gmünd, Zentrum Innere Medizin

Mutlangen, , Germany

Hämatologisch-Onkologische Gemeinschaftspraxis

München, , Germany

Gemeinschaftspraxis Hämatologie/ Onkologie

München, , Germany

MHP Münchener Hämatologie Praxis

München, , Germany

Universitätsklinikum Grosshadern LMU München

München, , Germany

Klinikum rechts der Isar, III. Medizinische Klinik und Poliklinik

München, , Germany

Hämatologisch-Onkologische Schwerpunktpraxis

München, , Germany

Onkologische und hämatologische Schwerpunktpraxis

Neumarkt, , Germany

MVZ I des Klinikums Nürnberg

Nuremberg, , Germany

Klinikum Oldenburg Klinik für Onkologie und Hämatologie / Innere Medizin II

Oldenburg, , Germany

Brüderkrankenhaus St. Josef Paderborn

Paderborn, , Germany

Klinikum Passau, II. Medizinische Klinik

Passau, , Germany

MVZ für Blut- und Krebserkrankungen

Potsdam, , Germany

Klinikum Vest, Behandlungszentrum Recklinghausen, Medizinische Klinik III

Recklinghausen, , Germany

Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie

Regensburg, , Germany

Universitätsklinikum Regensburg Abteilung für Hämatologie und internistische Onkologie

Regensburg, , Germany

Kreiskliniken Reutlingen GmbH, Klinikum am Steinenberg, Medizinische Klinik I

Reutlingen, , Germany

Universitätsmedizin Rostock, ZIM II Klinik für Hämatologie, Onkologie und

Rostock, , Germany

Agaplesion Diakonieklinikum Rotenburg

Rotenburg (Wümme), , Germany

Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III: Sektion für Onkologie und Hämatologie

Schwäbisch Hall, , Germany

Leopoldina-Krankenhaus

Schweinfurt, , Germany

Klinikverbund Südwest, Kliniken Sindelfingen-Böblingen gGmbH

Sindelfingen, , Germany

Diakonie Klinikum Stuttgart, Medizinische Klinik

Stuttgart, , Germany

Klinikum Mutterhaus der Borromäerinnen

Trier, , Germany

Medizinische Universitätsklinik, Department für Innere Medizin GCP Studienzentrale der Abteilung 2

Tübingen, , Germany

Universitätsklinikum Ulm Klinik für Innere Medizin III

Ulm, , Germany

Medizinisches Versorgungszentrum GmbH

Weiden, , Germany

Dres. med. T. Kamp - R. Eckert Innere/Hämatologie/Onkologie

Wendlingen, , Germany

Rems-Murr-Klinik Winnenden

Winnenden, , Germany

Onkologische Gemeinschaftspraxis Würselen und Stolberg

Würselen, , Germany

Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik II

Würzburg, , Germany

Heinrich-Braun-Klinikum gGmbH

Zwickau, , Germany

Kantonspital Aarau AG

Aarau, , Switzerland

Kantonspital Baden

Baden, , Switzerland

Universitätsspital Basel

Basel, , Switzerland

IOSI; Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Hopitaux Universitaires de Genève

Geneva, , Switzerland

Département d'oncologie UNIL-CHUV

Lausanne, , Switzerland

Kantonsspital Baselland

Liestal, , Switzerland

Luzerner Kantonsspital

Lucerne, , Switzerland

Universitätsspital Zürich

Zurich, , Switzerland

Countries

Czechia; Germany; Switzerland

Other Identifiers

2010-024262-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CML V

Identifier Type: -

Identifier Source: org_study_id