Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00006285

Trial Description

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Title

Imatinib Continuation Versus Nilotinib 300 mg Twice Daily in Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase and Major Molecular Re-sponse (MMR) Without Molecular Response ≥ 4.5 Log (MR4.5) Receiving Imatinib at a Dose of 400 to 800 mg Daily. An Open-label, Randomised Multicenter Phase 3b Study to Determine the Confirmed Rate of Molecular Response ≥ 4 Log (MR4) at Two Years

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Trial Acronym

DECLINE

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URL of the Trial

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Brief Summary in Lay Language

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

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Brief Summary in Scientific Language

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).

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Organizational Data

  •   DRKS00006285
  •   2014/06/30
  •   2014/06/24
  •   yes
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Secondary IDs

  •   2013-000077-68 
  •   NCT02174445  (ClinicalTrials.gov)
  •   CAMN107ADE18T  (Prof. Dr. Nikolas von Bubnoff)
  •   2013-000077-68 
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Health Condition or Problem studied

  •   Chronic Myeloid Leukemia
  •   C92.1 -  Chronic myeloid leukaemia [CML], BCR/ABL-positive
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Interventions/Observational Groups

  •   Drug: Imatinib
  •   Drug: Nilotinib
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
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Primary Outcome

- Proportion of patients with confirmed MR4 after two years of study treatment; time frame: 2 years; Proportion of patients with confirmed MR4 at two years of study treatment in both treatment arms. Confirmed MR4 at two years is defined as either BCR-ABL ≤ 0.01% IS at 21 and 24 months or BCR-ABL ≤ 0.01% IS at 24 months and confirmation within six weeks

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Secondary Outcome

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2014/03/31
  •   132
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion 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.

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Exclusion Criteria

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

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Prof. Dr. Nikolas von Bubnoff
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    • Novartis
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  • start of 1:1-Block address scientific-contact
    • University Hospital Freiburg
    • Nikolas von Bubnoff, Professor 
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    • Nikolas von Bubnoff, Professor 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   89
  •   2017/04/26
* This entry means the parameter is not applicable or has not been set.