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AzTrials

Chronic Myeloid LeukemiaPhase 3TIGERNCT01657604

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

A Phase 3 study testing Peginterferon α2b and Nilotinib in people with Chronic Myeloid Leukemia, run by University of Jena at 112 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myeloid Leukemia
What is being tested?
Peginterferon α2b and Nilotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
717 participants
Where
112 sitesin 3 countries
Study dates
24 Aug 2012to 31 May 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 22Show fewer
  • 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

Trial locations and contacts

112 sites in 3 countries.

112 sites in 3 countries

Germany101 sites

  • Universitätsklinikum Aachen Medizinische Klinik IV

    Aachen, 52074

  • Gesundheitszentrum St. Marien GmbH, Onkologie/ Hämatologie Onkologisches Zentrum

    Amberg, 92224

  • MVZ am Klinikum Arnsberg GmbH, Hämatologie - Internistische Onkologie

    Arnsberg, 56755

  • Studienzentrum Drs. Klausmann

    Aschaffenburg, 63739

  • Klinikum Augsburg

    Augsburg, 86156

  • Klinikum Bayreuth GmbH

    Bayreuth, 95445

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

    Berlin, 12351

  • Charité CVK, CC14, Klinik für Hämatologie und Onkologie

    Berlin, 13353

  • Evangelisches Klinikum Bethel

    Bielefeld, 33611

  • Universitätsklinikum Bonn Med. Klinik und Poliklinik III, Hämatologie

    Bonn, 53111

  • Zentrum für Ambulante Hämatologie und Onkologie

    Bonn, 53113

  • Städtisches Klinikum Braunschweig gGmbh, Medizinische Klinik III - Hämatologie

    Braunschweig, 38114

  • Klinikum Bremen-Mitte gGmbH

    Bremen, 28177

  • DIAKO Ev. Diakonie-Krankenhaus gGmbH, Medizinische Klinik II

    Bremen, 28239

  • Klinikum Chemnitz gGmbH Klinik für Innere Medizin III

    Chemnitz, 09113

  • Universitätsklinikum Köln

    Cologne, 50937

  • Onkologische Schwerpunktpraxis

    Dresden, 01307

  • Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

    Dresden, 01307

  • Onkologisch-Hämatologische Schwerpunktpraxis

    Eisenach, 99817

  • Dr. med. Ulrich Hauch

    Erfurt, 99084

  • Onkologische Schwerpunktpraxis Erlangen, Onkologie, Hämatologie

    Erlangen, 91052

  • Universitätsklinikum Erlangen Medizinische Klinik 5 - Hämatologie und int. Onkologie

    Erlangen, 91054

  • St.-Antonius-Hospital, Klinik für Hämatologie Onkologie

    Eschweiler, 52249

  • Klinik für Hämatologie Universitätsklinikum Essen

    Essen, 45122

  • Klinikum der Goethe Universität

    Frankfurt, 60590

  • Universitätsklinikum Freiburg Abteilung Innere Medizin I - Hämatologie und Onkologie

    Freiburg im Breisgau, 79106

  • MVZ-Osthessen GmbH Klinikum Fulda Tumorklinik

    Fulda, 36043

  • Praxis Dr. med. Schmitt

    Gerlingen, 70839

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

    Goslar, 38642

  • Georg-August Universität Göttingen Abteilung Hämatologie und Onkologie

    Göttingen, 37075

  • Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere

    Greifswald, 17475

  • Internistische Gemeinschaftspraxis

    Güstrow, 18273

  • Katholisches Krankenhaus Hagen gem. GmbH, Klinik für Hämatologie und

    Hagen, 58095

  • Gemeinschaftspraxis Hämatologie und internistische

    Halle, 06110

  • Universitätsklinikum Halle (Saale)

    Halle, 06120

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

    Hamburg, 20099

  • Universitätsklinikum Hamburg- Eppendorf, Medizinische Klinik 2

    Hamburg, 20246

  • Evangelisches Krankenhaus Hamm

    Hamm, 59063

  • St. Barbara-Klinik, Standort St. Josef

    Hamm, 59075

  • Mediprojekt, Gesellschaft für Medizinstatistik und Projektentwicklung

    Hanover, 30171

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

    Hanover, 30625

  • Universitätsklinikum Heidelberg Innere Medizin V: Hämatologie, Onkologie und Rheumatologie

    Heidelberg, 69120

  • Internistische Gemeinschaftspraxis Heilbronn

    Heilbronn, 74072

  • St. Bernward Krankenhaus Hildesheim

    Hildesheim, 31134

  • Universitätsklinikum des Saarlandes Klinik für Innere Medizin I

    Homburg/ Saar, 66421

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

    Idar-Oberstein, 55743

  • MVZ Onkologie Ingolstadt

    Ingolstadt, 85049

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

    Jena, 07740

  • Westpfalz-Klinikum GmbH Innere 1

    Kaiserslautern, 67655

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

    Karlsruhe, 76133

  • St. Vincentius-Kliniken Karlsruhe

    Karlsruhe, 76137

  • Klinikum Kempten Oberallgäu gGmbH

    Kempten, 87439

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

    Kiel, 24116

  • InVO, Institut für Versorgungsforschung in der Onkologie

    Koblenz, 56068

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

    Krefeld, 47805

  • Onkologische Schwerpunktpraxis

    Kronach, 96317

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

    Lebach, 66822

  • Onkologisches Schwerpunktpraxis

    Leer, 26789

  • Universitätsklinikum Leipzig, Department für Innere Medizin

    Leipzig, 04103

  • Dr. Aldaoud - Dr. Schwarzer Forschungsgesellschaft mbH

    Leipzig, 04289

  • Krankenhausgesellschaft St. Vincenz mbH Limburg

    Limburg an der Lahn, 65549

  • Gemeinschaftspraxis Uhle, Müller, Kröning, Jentsch-Ullrich

    Magdeburg, 39104

  • Internistische Gemeinschaftspraxis Onkologie/Hämatologie

    Mainz, 55122

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

    Mainz, 55131

  • Mannheimer Onkologie Praxis

    Mannheim, 68161

  • Universitätsmedizin Mannheim III. Medizinische Klinik

    Mannheim, 68169

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

    Marburg, 35032

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

    Minden, 32429

  • Drs. Schmidt/Schauenberg Onkologie

    Muhr am See, 91735

  • Hämatologisch-Onkologische Gemeinschaftspraxis

    München, 80638

  • Gemeinschaftspraxis Hämatologie/ Onkologie

    München, 81241

  • MHP Münchener Hämatologie Praxis

    München, 81377

  • Universitätsklinikum Grosshadern LMU München

    München, 81377

  • Klinikum rechts der Isar, III. Medizinische Klinik und Poliklinik

    München, 81675

  • Hämatologisch-Onkologische Schwerpunktpraxis

    München, 81679

  • Stauferklinikum Schwäbisch Gmünd, Zentrum Innere Medizin

    Mutlangen, 73557

  • Onkologische und hämatologische Schwerpunktpraxis

    Neumarkt, 92318

  • MVZ I des Klinikums Nürnberg

    Nuremberg, 90419

  • Klinikum Oldenburg Klinik für Onkologie und Hämatologie / Innere Medizin II

    Oldenburg, 26133

  • Brüderkrankenhaus St. Josef Paderborn

    Paderborn, 33098

  • Klinikum Passau, II. Medizinische Klinik

    Passau, 94032

  • MVZ für Blut- und Krebserkrankungen

    Potsdam, 14467

  • Klinikum Vest, Behandlungszentrum Recklinghausen, Medizinische Klinik III

    Recklinghausen, 45657

  • Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie

    Regensburg, 93049

  • Universitätsklinikum Regensburg Abteilung für Hämatologie und internistische Onkologie

    Regensburg, 93053

  • Kreiskliniken Reutlingen GmbH, Klinikum am Steinenberg, Medizinische Klinik I

    Reutlingen, 72764

  • Universitätsmedizin Rostock, ZIM II Klinik für Hämatologie, Onkologie und

    Rostock, 18057

  • Agaplesion Diakonieklinikum Rotenburg

    Rotenburg (Wümme), 27356

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

    Schwäbisch Hall, 74523

  • Leopoldina-Krankenhaus

    Schweinfurt, 97422

  • Klinikverbund Südwest, Kliniken Sindelfingen-Böblingen gGmbH

    Sindelfingen, 71065

  • Diakonie Klinikum Stuttgart, Medizinische Klinik

    Stuttgart, 70176

  • Klinikum Mutterhaus der Borromäerinnen

    Trier, 54290

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

    Tübingen, 72076

  • Universitätsklinikum Ulm Klinik für Innere Medizin III

    Ulm, 89081

  • Medizinisches Versorgungszentrum GmbH

    Weiden, 92637

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

    Wendlingen, 73240

  • Rems-Murr-Klinik Winnenden

    Winnenden, 71334

  • Onkologische Gemeinschaftspraxis Würselen und Stolberg

    Würselen, 52146

  • Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik II

    Würzburg, 97080

  • Heinrich-Braun-Klinikum gGmbH

    Zwickau, 08060

Other trials in Germany

Switzerland10 sites

  • Kantonspital Aarau AG

    Aarau, 5001

  • Kantonspital Baden

    Baden, 5404

  • Universitätsspital Basel

    Basel, 4031

  • IOSI; Oncology Institute of Southern Switzerland

    Bellinzona, 6500

  • Inselspital Bern

    Bern, 3010

  • Hopitaux Universitaires de Genève

    Geneva, 1211

  • Département d'oncologie UNIL-CHUV

    Lausanne, 1011

  • Kantonsspital Baselland

    Liestal, 4410

  • Luzerner Kantonsspital

    Lucerne, 6000

  • Universitätsspital Zürich

    Zurich, 8091

Other trials in Switzerland

Czechia1 site

  • University Hospital and Masaryk University Brno

    Brno, 62500

Other trials in Czechia

About this study

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

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.

Read the 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.
Being tested
Peginterferon α2b, Nilotinib
Keywords
CML, Tasigna, Nilotinib, Interferon
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Peginterferon α2bDrug

    Also called Redipen

    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.

  • NilotinibDrug

    Also called Tasigna

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

Study groups in NCT01657604
Study groupRoleWhat they receive
Nilotinib+IFNExperimentalPatients 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.
Receives: Drug: Peginterferon α2b
NilotinibActive comparatorPatients will receive nilotinib 300 mg BID given as two 150 mg capsules twice daily.
Receives: Drug: Nilotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    rate of MMR 18 months after randomization for each study treatment

    Measured: at least 18 months after start of study treatment

  2. 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

    Measured: at least 12 months after stopping all therapy

Secondary outcomes (10)

  1. rate of CCyR and MMR

    Measured: at 12, 18 and 24 months after start of treatment

  2. Time to CCyR, MMR, MR4 and MR4.5

    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

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

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

    Measured: 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)

    Measured: at 12, 24 and 60 months after start of treatment

  5. Rate of patients off treatment for at least 6 months

    all patients and comparison of treatment arms

    Measured: at 60 months after start of treatment

  6. safety and tolerability profile of nilotinib in comparison with nilotinib+pegylated interferon alpha and pegylated interferon alpha

    the time of risk is the time while receiving the therapy plus 28 days thereafter

    Measured: time of first study treatment until 28 days after stop of study treatment (expected 36 months)

  7. patients compliance to nilotinib based therapies

    Measured: 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

    Measured: during induction therapy (until at least 24 months), during maintenance therapy (until at least 36 months)

  9. pharmacoeconomics of the treatment strategies

    Measured: after end of study (expected in December 2020) (up to 8 years)

  10. Overall Survival (OS)

    Measured: at 12, 24 and 60 months after start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2012 (estimated)
  2. Study start24 Aug 2012
  3. Primary completion31 May 2022
  4. Study completion31 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
717 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01657604
Sponsor's protocol ID
CML V
Other IDs
2010-024262-22
Acronym
TIGER
Status last verified
May 2023
First submitted
9 Jul 2012
Last updated
10 May 2023
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Peginterferon α2b and Nilotinib in people with Chronic Myeloid Leukemia, run by University of Jena at 112 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 112 sites in Germany, Switzerland, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MMR rate at 18 months of nilotinib monotherapy versus nilotinib+pegylated interferon alpha (time frame: at least 18 months after start of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01657604.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.

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