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Philadelphia Positive (Ph+) Chronic Myeloid LeukemiaPhase 3MACS1532NCT02115386

Trial to Evaluate the Improvement of Chronic Low-grade AEs in Patients With Ph+ CML With Optimal Response to Imatinib When Switched to Nilotinib

A Phase 3 study testing Nilotinib in people with Philadelphia Positive (Ph+) Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 1 site in Russia.

Terminated

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

Official record
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Trial summary

Primary Objective for this study is to evaluate changes in chronic low grade non-hematological adverse events experienced by patients who have been treated with at least 6 months of imatinib and who have not responded to supportive measures, when they are switched to nilotinib (CTCAE grading system). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nilotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteRussia
Study dates
17 Dec 2015to 31 Oct 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 ≥ 18 years of age 2. ECOG ≤ 2 3. Diagnosis of CML-CP < 15% blasts in peripheral blood and bone marrow
  • < 30% blasts plus promyelocytes in peripheral blood and bone marrow
  • < 20% basophiles in the peripheral blood
  • ≥ 100 x 109 /L platelets
  • No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly. 4. Minimal treatment duration before inclusion is 6 months. 5. Optimal response to imatinib at the time of inclusion according to LeukemiaNet 2009 criteria defined as:
  • Patients treated with imatinib for ≥6 and <12 months must be in MCR Patients treated with imatinib for ≥12 and <18 months must be in CCR
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  • Patients treated with imatinib for ≥18 months must be in MMR (MMR response defined either as 3 log reduction of bcr-abl/abl ratio or as 0,1% by IS). 6. Initial treatment with 400mg imatinib with current treatment with imatinib 400 or 300 mg QD 7. Imatinib dose interruptions are allowed prior to inclusion but should not exceed 28 consecutive days 8. Persistent Grade 1- 2 non-hematological adverse events for at least 2 months despite best supportive care. Toxicity was to be evaluated by treating physician using CTCAE criteria. 9. In case of several types of non-hematological AEs no one can exceed grade 2 and at least one should last at least 2 months. 10. Adequate end organ function defined by:
  • Total bilirubin < 1.5 x ULN
  • AST and ALT < 2.5 x ULN
  • Creatinine < 1.5 x ULN
  • Serum amylase and lipase ≤ 1.5x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related 11. Serum potassium, magnesium, phosphorus and calcium values within normal range or corrected to within normal limits with supplements prior to first dose of study medication. 12. Patients must have an imatinib washout period of at least 3 days and not to exceed 7 days prior to the first dose of nilotinib. 13. Ability to provide written informed consent prior to any study related screening procedures being done

Who cannot join

  • Patients who have experienced any Grade 3 or higher non-hematologic toxicity 30 days prior to screening
  • Loss of response (hematologic, cytogenetic, molecular) any time prior to inclusion
  • Prior accelerated phase or blast phase CML
  • Previously documented T315I mutation
  • Chromosomal abnormalities (trisomy 8) and/or clonal evolution other than Ph+.
  • Previous treatment with imatinib >400 mg any time prior to inclusion.
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  • Previous treatment with any other tyrosine kinase inhibitors except for only imatinib
  • Impaired cardiac function including any of the following:
  • LVEF < 45% as determined by echocardiogram reading or MUGA
  • Complete left bundle branch block
  • Long QT syndrome or a known family history of long QT syndrome
  • History or presence of clinically significant ventricular or atrial tachyarrhythmias
  • Clinically significant resting bradycardia (< 50 beats per minute)
  • QTcF > 450 msec on baseline ECG. If QTcF > 450 and electrolytes are not within normal ranges, electrolytes were to be corrected and then the patient re-screened for QTcF
  • Myocardial infarction within 1 year of starting study drug
  • Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension) 9. Patients receiving therapy with inhibitors of CYP3A4 or medications that prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug. 10. Treatment with strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort), that cannot be discontinued or switched to a different medication prior to starting study drug. 11. Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug. 12. History of acute pancreatitis within 1 year of study entry. 13. Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required). 14. Any other malignancy that is clinically significant or requires active intervention.
  • 15. Severe or uncontrolled medical conditions (i.e., uncontrolled diabetes, active or uncontrolled infection). 16. Acute or chronic liver or severe renal disease considered unrelated to cancer.
  • 17. History of significant congenital or acquired bleeding disorder unrelated to cancer.
  • 18. Previous radiotherapy to ≥ 25% of the bone marrow. 19. Major surgery within 4 weeks prior to Day 1 of study or patients who have not recovered from prior surgery. 20. Treatment with other investigational agents within 30 days of Day 1. 21. History of non-compliance to medical regimens or inability to grant consent 22. Women who are pregnant, breast feeding, or of childbearing potential without a negative urinary test at baseline

Trial locations and contacts

1 site in 1 country.

Russia1 site

  • Novartis Investigative Site

    Moscow, 125167

Other trials in Russia

About this study

Official title: Open-label Multicenter Trial to Evaluate the Improvement of Chronic Low-grade Adverse Events Experienced by Patients With Ph+ Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) With Optimal Response to Imatinib When Switched From Imatinib to Nilotinib Treatment

Primary Objective for this study is to evaluate changes in chronic low grade non-hematological adverse events experienced by patients who have been treated with at least 6 months of imatinib and who have not responded to supportive measures, when they are switched to nilotinib (CTCAE grading system).

Read the detailed description

Study was terminated by Novartis

Being tested
Nilotinib
Keywords
Ph+ CML, chronic myeloid leukemia
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.

  • NilotinibDrug

    supplied in 150 mg capsules to be taken orally

Study groups in NCT02115386
Study groupRoleWhat they receive
NilotinibExperimentalDosage was 300 mg BID daily taken orally without food.
Receives: Drug: Nilotinib

What is being measured

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

  1. Number of Participants With Improvement of Grades of Persistent Non-hematological Adverse Event (AE) for Grade 1 and 2 at 6 Months

    Improvement was defined as decreasing of grade of non-hematological toxicity from 2 to <2 or from 1 to <1. In case of multiple low-grade non-hematological toxicities improvement was defined as an improvement of at least one non-hematological AE and no worsening of any other persistent non-hematological AEs.

    Measured: at 6 month after switching from imatinib to nilotinib

Secondary outcomes (6)

  1. Number of Participants With Improvement of Grades of Persistent Non-hematological Adverse Event (AE) for Grade 1 and 2 at 3 Months

    Improvement was defined as decreasing of grade of non-hematological toxicity from 2 to <2 or from 1 to <1. In case of multiple low-grade non-hematological toxicities improvement was defined as an improvement of at least one non-hematological AE and no worsening of any other persistent non-hematological AEs.

    Measured: at 3 month after switching from imatinib to nilotinib

  2. Number of Participants With Complete Cytogenetic Response (CCyR)

    Cytogenetic response will be assessed as the percentage of Ph+ metaphases in the bone marrow and is defined as the following: Complete (CCyR) - 0% Ph+ metaphases.

    Measured: at months 6,12 and 24 after switching from imatinib to nilotinib

  3. Number of Participants With a Major Molecular Response

    MMR was defined as a ≥ 3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤ 0.1 % BCR-ABL/ABL % by international scale as measured by RQ-PCR, confirmed by duplicate analysis of the same sample. Molecular response was described for all time points except screening where response was estimated.

    Measured: Months 1, 3, 6, early termination

  4. Time to and Duration of CCyR and MMR After Switch From Imatinib to Nilotinib at 24 Months

    to evaluate time to achievement and duration of CCyR and MMR after switching from imatinib to nilotinib

    Measured: at 24 Months

  5. Time to First Improvement of Persistant Chronic Low-grade Non-hematologic AEs at 24 Months After Switch From Imatinib to Nilotinib

    Evaluate time to first improvement of low-grade non-hematologic adverse events, experienced by patients treated with imatinib and persistent despite of best supportive measures after switching to nilotinib therapy. Optimal improvement is defined as AE grade decreasing to 0.

    Measured: first improvement of AEs after switch to 24 Months

  6. Lisiting by Participant of EORTC-QLQ-C30 for Quality of Life

    EORTC-QLQ-C30 was administered to evaluate quality of life changes after switching to nilotinib. Scores ranged from 1 (very poor) to 6 (excellent)

    Measured: Screening, months 1, 3, 6, after switch to nilotinib

Timeline

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

  1. First posted16 Apr 2014 (estimated)
  2. Study start17 Dec 2015
  3. Primary completion31 Oct 2016
  4. Study completion31 Oct 2016

Why it stopped: Study was terminated by Novartis

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02115386
Sponsor's protocol ID
CAMN107ARU02
Acronym
MACS1532
Status last verified
Dec 2019
First submitted
14 Apr 2014
Last updated
10 Dec 2019
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nilotinib in people with Philadelphia Positive (Ph+) Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 1 site in Russia.

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 19 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 10 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 1 site in Russia. 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?

Yes. Results are posted in the registry (first posted 10 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Improvement of Grades of Persistent Non-hematological Adverse Event (AE) for Grade 1 and 2 at 6 Months (time frame: at 6 month after switching from imatinib to nilotinib). 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 NCT02115386.

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 Dec 2019; AzTrials last refreshed its copy on 7 Nov 2026.

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