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Chronic Myeloid LeukemiaPhase 3DECLINENCT02174445

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

A Phase 3 study testing Imatinib and Nilotinib in people with Chronic Myeloid Leukemia, run by Prof. Dr. Nikolas von Bubnoff at 18 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 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?
Imatinib and Nilotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
18 sitesGermany
Study dates
Mar 2014to Oct 2019
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

  • Signed written informed consent
  • Male or female patients aged >=18 years (without upper limit of age)
  • ECOG performance status of 0 to 2
  • 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
  • Pretreatment with Imatinib with a treatment duration of at least 18 months at a dosage of 400 to 800 mg daily
  • 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
  • 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
  • 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.

Who cannot join

  • Any previous treatment for CML other than Hydroxyurea, Imatinib or Interferon alpha
  • Evidence of features of accelerated or blast phase at any time
  • Previous loss of hematologic or cytogenetic response
  • Concomitant medications known to be strong inducers or inhibitors of P450 Isoenzyme CYP3A4
  • Finding of a secondary BCR-ABL resistance mutation at any time
  • 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
Show all 28Show fewer
  • Patients who had prior allogeneic, syngeneic, or autologous bone mar-row transplant or stem cell transplant
  • 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
  • History of pancreatitis, chronic inflammatory diseases or autoimmune diseases
  • Patients who underwent solid organ transplantation
  • 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)
  • Known HIV and/or hepatitis B or C infection (testing is not mandatory)
  • 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
  • Women who are pregnant or breast feeding
  • Male/female patients of reproductive potential unwilling to practice a highly effective method of birth control
  • History of noncompliance to medical regimens
  • Treatment with another investigational product during this study or during the last 30 days prior to informed consent

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

Germany18 sites

  • Universitätsklinikum Aachen

    Aachen, 52074

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

    Augsburg, 86150

  • Universitätsklinikum Bonn

    Bonn, 53105

  • Universitätsklinik Köln

    Cologne, 50937

  • Gemeinschaftspraxis

    Dresden, 01307

  • Praxis Dr. Hauch

    Erfurt, 99084

  • Internistische Schwerpunktpraxis Erlangen oncosearch

    Erlangen, 91052

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

    Essen, 45136

  • University Medical Center

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Universitätsklinikum Jena

    Jena, 07747

  • Gemeinschaftspraxis Hämatologie/Onkologie

    Magdeburg, 39104

  • Klinikum Mannheim GmbH Universitätsklinikum

    Mannheim, 68167

  • Klinikum rechts der Isar, Technische Universität München

    München, 81675

  • Überörtliche Gemeinschaftspraxis Hämato-Onkologie Pasing/Fürstenfeldbruck

    Munich, 81241

  • Onkologische Praxis Oldenburg

    Oldenburg, 26121

  • Medizinische Statistik Saarbrücken, GbR

    Saarbrücken, 66113

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official 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

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

Read the 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).

Being tested
Imatinib, Nilotinib
Keywords
Patients with CML in chronic phase, Imatinib, Nilotinib
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.

  • ImatinibDrug

    Also called Glivec

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

  • NilotinibDrug

    Also called Tasigna

    300mg p.o., twice-daily

Study groups in NCT02174445
Study groupRoleWhat they receive
ImatinibExperimentalImatinib 400-800mg, daily, maximum 6 years
Receives: Drug: Imatinib
NilotinibActive comparatorNilotinib, 300mg, twice daily, maximum 6 years
Receives: Drug: Nilotinib

What is being measured

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

  1. Proportion of patients with confirmed MR4 after two years of study treatment

    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

    Measured: 2 years

Timeline

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

  1. First posted25 Jun 2014 (estimated)
  2. Study startMar 2014
  3. Primary completionDec 2018
  4. Study completionOct 2019

Why it stopped: very slow recruitment rate and a lot of pat. didn't fulfil BCR-ABL requirements

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02174445
Sponsor's protocol ID
CAMN107ADE18T
Other IDs
2013-000077-68, DRKS00006285
Acronym
DECLINE
Status last verified
Nov 2019
First submitted
24 Jun 2014
Last updated
2 Dec 2019
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Imatinib and Nilotinib in people with Chronic Myeloid Leukemia, run by Prof. Dr. Nikolas von Bubnoff at 18 sites in Germany.

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 8 inclusion and 28 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: stopped early, as of the sponsor's last update on 2 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Germany. 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 was stopped early (reason given: very slow recruitment rate and a lot of pat. didn't fulfil BCR-ABL requirements). Results are not available in the source record.

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?

Proportion of patients with confirmed MR4 after two years of study treatment (time frame: 2 years). 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 NCT02174445.

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 2 Dec 2019.

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