An Open-label, Randomised Multicenter Phase 3b Study to Determine the Confirmed Rate of Molecular Response ≥ 4 Log (MR4) at Two Years

NCT ID: NCT02174445

Last Updated: 2019-12-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2019-10-31

Brief Summary

This is an open-label, multicenter, randomised phase 3b clinical trial of Imatinib 400 to 800 mg daily versus Nilotinib 300 mg two times daily in chronic phase CML patients with confirmed MMR without MR4.5

Detailed Description

This is an open-label, multicenter, randomised phase 3b clinical trial of Imatinib 400 to 800 mg daily versus Nilotinib 300 mg two times daily in chronic phase CML patients with confirmed MMR without MR4.5 (after having received Imatinib 400 to 800 mg daily for at least 18 months) to determine the proportion of patients with confirmed MR4 after two years. Patients in treatment arm A (Imatinib) who do not achieve confirmed MR4 2 years after randomisation will be offered cross-over from Imatinib 400 to 800 mg daily to Nilotinib 300 mg twice daily. One hundred thirty-two (132) patients will be included and randomised 1:1 to each treatment arm.

The study will be stratified by duration of Imatinib treatment before screen-ing (≤36 months / >36 months) as well as by the level of response at inclusion (MMR / MR4).

Conditions

Chronic Myeloid Leukemia

Study Design

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

Study Groups

Imatinib

Imatinib 400-800mg, daily, maximum 6 years

Group Type: EXPERIMENTAL

Imatinib

Intervention Type: DRUG

Imatinib, 400 to 800 mg p.o., daily

Nilotinib

Nilotinib, 300mg, twice daily, maximum 6 years

Group Type: ACTIVE_COMPARATOR

Nilotinib

Intervention Type: DRUG

300mg p.o., twice-daily

Interventions

Imatinib

Imatinib, 400 to 800 mg p.o., daily

Intervention Type: DRUG

Nilotinib

300mg p.o., twice-daily

Intervention Type: DRUG

Other Intervention Names

Glivec; Tasigna

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent

2. Male or female patients aged >=18 years (without upper limit of age)

3. ECOG performance status of 0 to 2

4. CML in chronic phase, with chronic phase defined as blasts < 15% in blood and/or bone marrow and peripheral blood basophils < 20% and platelets ≥ 100 G/L

5. Pretreatment with Imatinib with a treatment duration of at least 18 months at a dosage of 400 to 800 mg daily

6. Major molecular response (MMR) without molecular response ≥ 4.5 log (MR4.5), i.e. BCR-ABL>0.0032% and ≤0.1% IS confirmed by central la-boratory at screening will be required for randomisation

7. Patients must have a serum Creatinine of ≤ 1.5 x ULN, SGOT ≤ 1.5 x ULN, total bilirubin ≤ 1.5 x ULN (except known M. Gilbert), and Lipase ≤ 1.5 x ULN

8. Women of child-bearing potential defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months, must have a negative serum pregnancy test during screening period. Male and fe-male patients of reproductive potential must agree to employ highly ef-fective methods of birth control throughout the study and for up to 3 months following discontinuation of study drug. Appropriate methods are e.g. a highly effective method of first choice, i.e. a method with a low failure rate (less than 1% per year) like sexual abstinence, com-bined oral contraceptives, implants, injectable, some Intra Uterine Devices (IUDs), vasectomized partner, in combination with a method of second choice like condom, diaphragm, or cup pessary with spermicidal foam/gel/film/cream/suppository.

Exclusion Criteria

1. Any previous treatment for CML other than Hydroxyurea, Imatinib or Interferon alpha

2. Evidence of features of accelerated or blast phase at any time

3. Previous loss of hematologic or cytogenetic response

4. Concomitant medications known to be strong inducers or inhibitors of P450 Isoenzyme CYP3A4

5. Finding of a secondary BCR-ABL resistance mutation at any time

6. History of intolerance to Imatinib that required treatment interruption longer than 4 weeks (cumulative) or dose reductions to less than 400 mg daily for longer than 4 weeks (cumulative) during the last 12 months before informed consent

7. Patients who had prior allogeneic, syngeneic, or autologous bone mar-row transplant or stem cell transplant

8. Patients unwilling to or unable to comply with the planned therapeutic intervention or to comply with the study treatment visits including blood sample collection within the protocol

9. History of pancreatitis, chronic inflammatory diseases or autoimmune diseases

10. Patients who underwent solid organ transplantation

11. Impaired cardiac function, including any of the following:

• History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemi block, bifascicular block in screening ECG
• Use of a cardiac pacemaker
• ST depression of > 1mm in 2 or more leads and/or T wave inver-sions in 2 or more contiguous leads in screening ECG
• Congenital Long QT Syndrome
• QTc> 450 msec in the screening ECG
• QT prolonging concomitant medication
• History of or presence of significant ventricular or atrial tachy-arrhythmia in screening ECG
• History of or presence of clinically significant resting bradycardia (< 50 beats per minute)
• Myocardial infarction within 12 months prior to informed consent
• Unstable angina diagnosed or treated during the past 12 months before informed consent
• Other clinically significant heart disease (e.g., congestive heart fail-ure, uncontrolled hypertension, history of labile hypertension)

12. Known HIV and/or hepatitis B or C infection (testing is not mandatory)

13. Other malignancies within the past 3 years before informed consent except for adequately treated carcinoma of the cervix and basal or squamous cell carcinoma of the skin

14. Women who are pregnant or breast feeding

15. Male/female patients of reproductive potential unwilling to practice a highly effective method of birth control

16. History of noncompliance to medical regimens

17. Treatment with another investigational product during this study or during the last 30 days prior to informed consent

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

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Prof. Dr. Nikolas von Bubnoff

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Nikolas von Bubnoff

Mr.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nikolas von Bubnoff, Professor

Role: PRINCIPAL_INVESTIGATOR

University Hospital Freiburg

Locations

Universitätsklinikum Aachen

Aachen, , Germany

Praxis Dr. Bruder / Dr. Heinrich / Prof. Bangerter

Augsburg, , Germany

Universitätsklinikum Bonn

Bonn, , Germany

Universitätsklinik Köln

Cologne, , Germany

Gemeinschaftspraxis

Dresden, , Germany

Praxis Dr. Hauch

Erfurt, , Germany

Internistische Schwerpunktpraxis Erlangen oncosearch

Erlangen, , Germany

Praxis für Hämatologie/Onkologie Dres. Rudolph, Sengpiel, von Verschuer

Essen, , Germany

University Medical Center

Freiburg im Breisgau, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitätsklinikum Jena

Jena, , Germany

Gemeinschaftspraxis Hämatologie/Onkologie

Magdeburg, , Germany

Klinikum Mannheim GmbH Universitätsklinikum

Mannheim, , Germany

Überörtliche Gemeinschaftspraxis Hämato-Onkologie Pasing/Fürstenfeldbruck

Munich, , Germany

Klinikum rechts der Isar, Technische Universität München

München, , Germany

Onkologische Praxis Oldenburg

Oldenburg, , Germany

Medizinische Statistik Saarbrücken, GbR

Saarbrücken, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Countries

Germany

Other Identifiers

2013-000077-68

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRKS00006285

Identifier Type: REGISTRY

Identifier Source: secondary_id

CAMN107ADE18T

Identifier Type: -

Identifier Source: org_study_id