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

NCT01657604 | Completed Phase 3 DMC

• 2 other identifiers: CML V2010-024262-22
• Study Type: interventional
• Target: 717
• Locations: 3 countries
• Sites: 112

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.

Conditions

Chronic Myeloid Leukemia

Keywords

CML; Tasigna; Nilotinib; Interferon

Outcome Measures

Primary Outcomes (2)

• MMR rate at 18 months of nilotinib monotherapy versus nilotinib+pegylated interferon alpha

  rate of MMR 18 months after randomization for each study treatment

  at least 18 months after start of study treatment

• rate of continuous MMR after discontinuation of nilotinib versus pegylated interferon alpha

  rate of patients with molecular relapse (loss of MMR) 12 months after discontinuation of any treatment for CML

  at least 12 months after stopping all therapy

Secondary Outcomes (10)

• rate of CCyR and MMR

  at 12, 18 and 24 months after start of treatment

• Time to CCyR, MMR, MR4 and MR4.5

  date of randomization until time to endpoints or end of study duration (at least 36 months)

• rate of MR4 and MR4.5 during maintenance therapy and after discontinuation

  start of maintenance therapy (after at least 24 months of treatment) until end of study duration (at least 36 months)

• Progression-Free Survival (PFS)

  at 12, 24 and 60 months after start of treatment

• Rate of patients off treatment for at least 6 months

  at 60 months after start of treatment

Study Arms (2)

Nilotinib+IFN

EXPERIMENTAL

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

Nilotinib

ACTIVE COMPARATOR

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

Drug: Nilotinib

Interventions

Peginterferon α2b 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.

Also known as: Redipen

Nilotinib+IFN

Nilotinib 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.

Also known as: Tasigna

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Jena: lead

Study Sites (112)

University Hospital and Masaryk University Brno

Brno, 62500, Czechia

Location

Universitätsklinikum Aachen Medizinische Klinik IV

Aachen, 52074, Germany

Location

Gesundheitszentrum St. Marien GmbH, Onkologie/ Hämatologie Onkologisches Zentrum

Amberg, 92224, Germany

Location

MVZ am Klinikum Arnsberg GmbH, Hämatologie - Internistische Onkologie

Arnsberg, 56755, Germany

Location

Studienzentrum Drs. Klausmann

Aschaffenburg, 63739, Germany

Location

Klinikum Augsburg

Augsburg, 86156, Germany

Location

Klinikum Bayreuth GmbH

Bayreuth, 95445, Germany

Location

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

Berlin, 12351, Germany

Location

Charité CVK, CC14, Klinik für Hämatologie und Onkologie

Berlin, 13353, Germany

Location

Evangelisches Klinikum Bethel

Bielefeld, 33611, Germany

Location

Universitätsklinikum Bonn Med. Klinik und Poliklinik III, Hämatologie

Bonn, 53111, Germany

Location

Zentrum für Ambulante Hämatologie und Onkologie

Bonn, 53113, Germany

Location

Städtisches Klinikum Braunschweig gGmbh, Medizinische Klinik III - Hämatologie

Braunschweig, 38114, Germany

Location

Klinikum Bremen-Mitte gGmbH

Bremen, 28177, Germany

Location

DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II

Bremen, 28239, Germany

Location

Klinikum Chemnitz gGmbH Klinik für Innere Medizin III

Chemnitz, 09113, Germany

Location

Universitätsklinikum Köln

Cologne, 50937, Germany

Location

Onkologische Schwerpunktpraxis

Dresden, 01307, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Onkologisch-Hämatologische Schwerpunktpraxis

Eisenach, 99817, Germany

Location

Dr. med. Ulrich Hauch

Erfurt, 99084, Germany

Location

Onkologische Schwerpunktpraxis Erlangen, Onkologie, Hämatologie

Erlangen, 91052, Germany

Location

Universitätsklinikum Erlangen Medizinische Klinik 5 - Hämatologie und int. Onkologie

Erlangen, 91054, Germany

Location

St.-Antonius-Hospital, Klinik für Hämatologie Onkologie

Eschweiler, 52249, Germany

Location

Klinik für Hämatologie Universitätsklinikum Essen

Essen, 45122, Germany

Location

Klinikum der Goethe Universität

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg Abteilung Innere Medizin I - Hämatologie und Onkologie

Freiburg im Breisgau, 79106, Germany

Location

MVZ-Osthessen GmbH Klinikum Fulda Tumorklinik

Fulda, 36043, Germany

Location

Praxis Dr. med. Schmitt

Gerlingen, 70839, Germany

Location

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

Goslar, 38642, Germany

Location

Georg-August Universität Göttingen Abteilung Hämatologie und Onkologie

Göttingen, 37075, Germany

Location

Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere

Greifswald, 17475, Germany

Location

Internistische Gemeinschaftspraxis

Güstrow, 18273, Germany

Location

Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und

Hagen, 58095, Germany

Location

Gemeinschaftspraxis Hämatologie und internistische

Halle, 06110, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, 06120, Germany

Location

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

Hamburg, 20099, Germany

Location

Universitätsklinikum Hamburg- Eppendorf, Medizinische Klinik 2

Hamburg, 20246, Germany

Location

Evangelisches Krankenhaus Hamm

Hamm, 59063, Germany

Location

St. Barbara-Klinik, Standort St. Josef

Hamm, 59075, Germany

Location

Mediprojekt, Gesellschaft für Medizinstatistik und Projektentwicklung

Hanover, 30171, Germany

Location

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

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg Innere Medizin V: Hämatologie, Onkologie und Rheumatologie

Heidelberg, 69120, Germany

Location

Internistische Gemeinschaftspraxis Heilbronn

Heilbronn, 74072, Germany

Location

St. Bernward Krankenhaus Hildesheim

Hildesheim, 31134, Germany

Location

Universitätsklinikum des Saarlandes Klinik für Innere Medizin I

Homburg/ Saar, 66421, Germany

Location

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

Idar-Oberstein, 55743, Germany

Location

MVZ Onkologie Ingolstadt

Ingolstadt, 85049, Germany

Location

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

Jena, 07740, Germany

Location

Westpfalz-Klinikum GmbH Innere 1

Kaiserslautern, 67655, Germany

Location

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

Karlsruhe, 76133, Germany

Location

St. Vincentius-Kliniken Karlsruhe

Karlsruhe, 76137, Germany

Location

Klinikum Kempten Oberallgäu gGmbH

Kempten, 87439, Germany

Location

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

Kiel, 24116, Germany

Location

InVO, Institut für Versorgungsforschung in der Onkologie

Koblenz, 56068, Germany

Location

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

Krefeld, 47805, Germany

Location

Onkologische Schwerpunktpraxis

Kronach, 96317, Germany

Location

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

Lebach, 66822, Germany

Location

Onkologisches Schwerpunktpraxis

Leer, 26789, Germany

Location

Universitätsklinikum Leipzig, Department für Innere Medizin

Leipzig, 04103, Germany

Location

Dr. Aldaoud - Dr. Schwarzer Forschungsgesellschaft mbH

Leipzig, 04289, Germany

Location

Krankenhausgesellschaft St. Vincenz mbH Limburg

Limburg an der Lahn, 65549, Germany

Location

Gemeinschaftspraxis Uhle, Müller, Kröning, Jentsch-Ullrich

Magdeburg, 39104, Germany

Location

Internistische Gemeinschaftspraxis Onkologie/Hämatologie

Mainz, 55122, Germany

Location

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

Mainz, 55131, Germany

Location

Mannheimer Onkologie Praxis

Mannheim, 68161, Germany

Location

Universitätsmedizin Mannheim III. Medizinische Klinik

Mannheim, 68169, Germany

Location

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

Marburg, 35032, Germany

Location

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

Minden, 32429, Germany

Location

Drs. Schmidt/Schauenberg Onkologie

Muhr am See, 91735, Germany

Location

Stauferklinikum Schwäbisch Gmünd, Zentrum Innere Medizin

Mutlangen, 73557, Germany

Location

Hämatologisch-Onkologische Gemeinschaftspraxis

München, 80638, Germany

Location

Gemeinschaftspraxis Hämatologie/ Onkologie

München, 81241, Germany

Location

MHP Münchener Hämatologie Praxis

München, 81377, Germany

Location

Universitätsklinikum Grosshadern LMU München

München, 81377, Germany

Location

Klinikum rechts der Isar, III. Medizinische Klinik und Poliklinik

München, 81675, Germany

Location

Hämatologisch-Onkologische Schwerpunktpraxis

München, 81679, Germany

Location

Onkologische und hämatologische Schwerpunktpraxis

Neumarkt, 92318, Germany

Location

MVZ I des Klinikums Nürnberg

Nuremberg, 90419, Germany

Location

Klinikum Oldenburg Klinik für Onkologie und Hämatologie / Innere Medizin II

Oldenburg, 26133, Germany

Location

Brüderkrankenhaus St. Josef Paderborn

Paderborn, 33098, Germany

Location

Klinikum Passau, II. Medizinische Klinik

Passau, 94032, Germany

Location

MVZ für Blut- und Krebserkrankungen

Potsdam, 14467, Germany

Location

Klinikum Vest, Behandlungszentrum Recklinghausen, Medizinische Klinik III

Recklinghausen, 45657, Germany

Location

Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie

Regensburg, 93049, Germany

Location

Universitätsklinikum Regensburg Abteilung für Hämatologie und internistische Onkologie

Regensburg, 93053, Germany

Location

Kreiskliniken Reutlingen GmbH, Klinikum am Steinenberg, Medizinische Klinik I

Reutlingen, 72764, Germany

Location

Universitätsmedizin Rostock, ZIM II Klinik für Hämatologie, Onkologie und

Rostock, 18057, Germany

Location

Agaplesion Diakonieklinikum Rotenburg

Rotenburg (Wümme), 27356, Germany

Location

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

Schwäbisch Hall, 74523, Germany

Location

Leopoldina-Krankenhaus

Schweinfurt, 97422, Germany

Location

Klinikverbund Südwest, Kliniken Sindelfingen-Böblingen gGmbH

Sindelfingen, 71065, Germany

Location

Diakonie Klinikum Stuttgart, Medizinische Klinik

Stuttgart, 70176, Germany

Location

Klinikum Mutterhaus der Borromäerinnen

Trier, 54290, Germany

Location

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

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm Klinik für Innere Medizin III

Ulm, 89081, Germany

Location

Medizinisches Versorgungszentrum GmbH

Weiden, 92637, Germany

Location

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

Wendlingen, 73240, Germany

Location

Rems-Murr-Klinik Winnenden

Winnenden, 71334, Germany

Location

Onkologische Gemeinschaftspraxis Würselen und Stolberg

Würselen, 52146, Germany

Location

Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik II

Würzburg, 97080, Germany

Location

Heinrich-Braun-Klinikum gGmbH

Zwickau, 08060, Germany

Location

Kantonspital Aarau AG

Aarau, 5001, Switzerland

Location

Kantonspital Baden

Baden, 5404, Switzerland

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

IOSI; Oncology Institute of Southern Switzerland

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Genève

Geneva, 1211, Switzerland

Location

Département d'oncologie UNIL-CHUV

Lausanne, 1011, Switzerland

Location

Kantonsspital Baselland

Liestal, 4410, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

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

Study Officials

• Andreas Hochhaus, Prof. MD

  Jena University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Dept. Hematology/Oncology

Study Record Dates

• First Submitted: July 9, 2012
• First Posted: August 6, 2012
• Study Start: August 24, 2012
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: May 10, 2023

Record last verified: 2023-05

Locations

CH (10); CZ (1); DE (101)