Philidelphia Positive Chronic Myeloid LeukaemiaPhase 3ENESTswiftNCT02108951

Study to Assess Efficacy and Safety of Nilotinib 300mg Twice Daily in Patients With Philadelphia Positive Chronic Myeloid Leukaemia (CML) in Chronic Phase Who Are Intolerant to Prior Tyrosine Kinase Inhibitors.

A Phase 3 study testing Nilotinib in people with Philidelphia Positive Chronic Myeloid Leukaemia, run by Novartis Pharmaceuticals at 14 sites in Australia.

Terminated

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

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Philidelphia Positive Chronic Myeloid Leukaemia
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: 20 participants
Where: 14 sitesAustralia
Study dates: 7 Jul 2014to 10 Aug 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

Written informed consent prior to screening procedures
Eastern Cooperative Oncology Grou (ECOG) Performance Status of 0, 1, or 2.
Patient with diagnosis of Ph+ CML-CP associated with BCR-ABL quantifiable by RQ-PCR (IS).
Patient has received a minimum of 3 months of imatinib or dasatinib treatment (any dose) since initial diagnosis with a documented response.
Patient is eligible for Pharmaceutical Benefits Scheme (PBS) reimbursed 1st line TKI treatment.
Patient has experienced non-hematological Adverse Events (AE(s)) of any grade, which persisted for at least 1 month despite supportive care or recurred at any grade at least once. Patients who, at the Investigator's discretion, require immediate discontinuation due to the severity of the adverse event are also eligible.

Show all 10Show fewer

No other current or planned anti-leukemia therapies.
Adequate organ function.
Potassium, Magnesium and Total Calcium above Lower limit of normal.
life expectancy of more than 12 months in the absence of any intervention

Who cannot join

Prior treatment with nilotinib.
Prior Accelerated Phase (AP), Blast Crisis (BC) or allogeneic-transplant (unless the patient received an autologous transplant and was in Chrionic Phase (CP) prior to transplant and never in AP or BC).
Patient has documented Molecular Response (MR) 4.5 at the time of study entry
Patients with atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.
Known impaired cardiac function.
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
Pregnant or breast feeding (lactating) women.
Women of child-bearing potential unwilling or unable to use highly effective contraception.

Trial locations and contacts

14 sites in 1 country.

City, postcode or hospital

14 sites in 1 country

Australia14 sites

Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Canberra, Australian Capital Territory, 2605
Novartis Investigative Site
Douglas, Queensland, 4810
Novartis Investigative Site
Fitzroy, Victoria, 3065
Novartis Investigative Site
Geelong, Victoria, 3220
Novartis Investigative Site
Kingswood, New South Wales, 2747
Novartis Investigative Site
Kogarah, New South Wales, 2217
Novartis Investigative Site
Liverpool, New South Wales, 2170
Novartis Investigative Site
Melbourne, Victoria, 3000
Novartis Investigative Site
Murdoch, Western Australia, 6150
Novartis Investigative Site
Nambour, Queensland, 4560
Novartis Investigative Site
Nedlands, Western Australia, 6009
Novartis Investigative Site
South Brisbane, Queensland, 4101
Novartis Investigative Site
St Leonards, New South Wales, 2065

Other trials in Australia

About this study

Official title: A Multicenter, Single Arm Study to Assess Efficacy and Safety of Nilotinib 300mg Twice Daily in Patients With Philadelphia Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP) Who Are Intolerant to Prior Tyrosine Kinase Inhibitors (TKIs).

The purpose of this Australian study was to assess the efficacy and safety of nilotinib 300mg twice daily in patients with chronic myeloid leukemia chronic phase who were intolerant but responsive to 1st line treatment with imatinib or dasatinib. Eligible patients have been previously treated with imatinib or dasatinib for at least 3 months and are experiencing non-hematologic toxicity whilst having documented responses that meet PBS authority for 1st line treatment of CML without current MR4.5.

Read the detailed description

The study was planned to enroll 130 patients to achieve the sample size requirement for a meaning full conclusion. Study got terminated with 20 patients because of slow recruitment. Therefore, due to small sample size, the results cannot be considered clinical significant.

Conditions: Philidelphia Positive Chronic Myeloid Leukaemia
Being tested: Nilotinib
Keywords: CML, Ph-CML, leukaemia, leukemia, chronic myeloid leukemia, chronic myeloid leukaemia, TKI intolerance, tyrosine kinase inhibitor, tyrosine kinase inhibitor intolerance
Medical subject headings: Leukemia, 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
Also called AMN107
Nilotinib 150mg hard gelatin capsules taken orally

Study groups in NCT02108951
Study group	Role	What they receive
Nilotinib	Experimental	Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study. Receives: Drug: Nilotinib

What is being measured

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

Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy.
MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Measured: Baseline, 96 weeks (24 months)
Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months
Molecular Response (MR4.0) rate is defined as the percentage of patients who have achieved a 4-log reduction in BCR-ABL levels at 12 months and 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy.
MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 X the baseline value, the patients were classified as achieving a 1 log reduction in BCR-ABL.
Measured: Baseline, 48 weeks (12 months), 96 weeks (24 months)
Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months
Major Molecular Response (MMR) rate is defined as the percentage of patients who have achieved a 3 log reduction in BCR-ABL levels at 12 months and at 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood at the 12 and 24 months following the commencement of nilotinib therapy. MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 * the baseline Value, the patient will be classified as achieving a 1 log drop.
Measured: Baseline, 48 weeks (12 months), 96 weeks (24 months)
Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months
Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy.
Deep molecular response (MR4.5) rate was defined as the percentage of patients who have achieved a 4.5-log reduction (MR4.5) in BCR-ABL levels during the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Measured: Baseline, 96 weeks (24 months)
Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy.
MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Measured: Baseline, 96 weeks (24 months)

Secondary outcomes (9)

Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
No response corresponds to a BCR-ABL ratio < 0.1% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Measured: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Measured: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72 and 96
Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Measured: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Measured: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5)
Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels is measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a
BCR-ABL ratio 0.0032% IS using RQ-PCR. The derivation of time to molecular response for patients in the study was measured from the date of first nilotinib use, defined as follows:
Days to MR4.5 = date of assessment where BCR-ABL ratio is 0.0032% IS - date of baseline + 1.
Measured: 96 weeks (24 months)
Time to Progression-free Survival (PFS)
PFS was defined as the time from the date of baseline visit to the date of earliest progression-defining event: namely progression (or withdrawal due to progression to blast crisis (BC) or accelerated phase (AP) disease), or death from any cause.
Patients who did not progress were censored at earliest of the following:
- the date of the 24-month visit;
- the date of loss to follow-up;
- the date of discontinuation of study treatment for any reason other than progression to BC, or AP disease, or death
Measured: 96 weeks (24 months)
Time to Event Free Survival (EFS)
EFS was defined as the time from date of baseline visit to the first occurrence of any of the following: Disease progression, treatment failure or death from any cause, whichever was earlier. Patients who did not have an event of interest were censored at earliest of the following:
- the date of the 24-month visit;
- the date of loss to follow-up;
- the date of withdrawal from the study for any reason other than lack of efficacy/progressive disease, tolerance to reduced dose or death
Measured: 96 weeks (24 months)
Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit
The total number of patients that have showed improvement with respect to CTCAE grades at the time of the 12-week visit are reported. Improved is defined as prior to, or at the time of the 12-week visit, the AE has completely resolved.
Measured: Baseline, week 12 (month 3)
Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Quality of life was assessed using the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) self-administered questionnaire for adult CML patients. The questionnaire consisted of 13 core questions in part I measuring the severity of symptoms, 6 questions in part 2 assessing the interference of symptoms on daily living. The CML component of the MDASI provided an additional 7 CML-specific symptom items: diarrhea, swelling, rash/skin change, muscle soreness/cramping, bruising/bleeding easily, malaise, and headache. In part I (13 questions) and the CML component (7 questions) each question was scored from 0 to 10 where 0 indicates a symptom is not present and 10 indicate the symptom is "as bad as you can imagine". For part 1 the total score can therefore range from 0 to 130 and for CML 0 to 70. Part 2 is also recorded on a 0 to 10 scale, but 0 now indicates that the symptom "did not interfere" and 10 "interfered completely". The total score can range from 0 to 60.
Measured: Baseline, week 12, 24, 48, 96

Timeline

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

7 Jul 201410 Aug 2016

First posted9 Apr 2014 (estimated)
Study start7 Jul 2014
Primary completion10 Aug 2016
Study completion10 Aug 2016

Why it stopped: Study was terminated because of slow recruitment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Philidelphia Positive Chronic Myeloid LeukaemiaStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02108951
Sponsor's protocol ID: CAMN107AAU04
Acronym: ENESTswift
Status last verified: Sep 2017
First submitted: 7 Apr 2014
Last updated: 27 Oct 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Single Arm Study to Assess Efficacy and Safety of Nilotinib 300mg Twice Daily in Patients With Philadelphia Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP) Who Are Intolerant to Prior Tyrosine Kinase Inhibitors (TKIs).
ClinicalTrials.gov ID: NCT02108951
Acronym / sponsor ID: ENESTswift / CAMN107AAU04
Conditions: Philidelphia Positive Chronic Myeloid Leukaemia
Keywords: CML, Ph-CML, leukaemia, leukemia, chronic myeloid leukemia, chronic myeloid leukaemia, TKI intolerance, tyrosine kinase inhibitor
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study was terminated because of slow recruitment
Enrolment: 20 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 7 Jul 2014 (actual)
Primary completion: 10 Aug 2016 (actual)
Study completion: 10 Aug 2016 (actual)
First posted: 9 Apr 2014 (estimated)
Results: Posted 27 Oct 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Nilotinib	Experimental	Drug: NilotinibNilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Written informed consent prior to screening procedures
Eastern Cooperative Oncology Grou (ECOG) Performance Status of 0, 1, or 2.
Patient with diagnosis of Ph+ CML-CP associated with BCR-ABL quantifiable by RQ-PCR (IS).
Patient has received a minimum of 3 months of imatinib or dasatinib treatment (any dose) since initial diagnosis with a documented response.
Patient is eligible for Pharmaceutical Benefits Scheme (PBS) reimbursed 1st line TKI treatment.

Key exclusion criteria (8 listed)

Prior treatment with nilotinib.
Prior Accelerated Phase (AP), Blast Crisis (BC) or allogeneic-transplant (unless the patient received an autologous transplant and was in Chrionic Phase (CP) prior to transplant and never in AP or BC).
Patient has documented Molecular Response (MR) 4.5 at the time of study entry
Patients with atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.
Known impaired cardiac function.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NilotinibAlso: AMN107Nilotinib 150mg hard gelatin capsules taken orally	Drug	Nilotinib

Primary outcome

Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month
Time frame: Baseline, 96 weeks (24 months)
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months
Time frame: Baseline, 48 weeks (12 months), 96 weeks (24 months)
Molecular Response (MR4.0) rate is defined as the percentage of patients who have achieved a 4-log reduction in BCR-ABL levels at 12 months and 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 X the baseline value, the patients were classified as achieving a 1 log reduction in BCR-ABL.
Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months
Time frame: Baseline, 48 weeks (12 months), 96 weeks (24 months)
Major Molecular Response (MMR) rate is defined as the percentage of patients who have achieved a 3 log reduction in BCR-ABL levels at 12 months and at 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood at the 12 and 24 months following the commencement of nilotinib therapy. MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 * the baseline Value, the patient will be classified as achieving a 1 log drop.
Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months
Time frame: Baseline, 96 weeks (24 months)
Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. Deep molecular response (MR4.5) rate was defined as the percentage of patients who have achieved a 4.5-log reduction (MR4.5) in BCR-ABL levels during the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
Time frame: Baseline, 96 weeks (24 months)
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is < 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.

9 secondary outcomes

Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Time frame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Time frame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72 and 96
Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Time frame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Time frame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5)
Time frame: 96 weeks (24 months)
Time to Progression-free Survival (PFS)
Time frame: 96 weeks (24 months)
Time to Event Free Survival (EFS)
Time frame: 96 weeks (24 months)
Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit
Time frame: Baseline, week 12 (month 3)
Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Time frame: Baseline, week 12, 24, 48, 96

Results and safety

Results posted to the registry on 27 Oct 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Nilotinib	20	4

Primary outcome: Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month

Time frame: Baseline, 96 weeks (24 months). Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Nilotinib n = 20
Value	50 (27.2 to 72.8)

Population analysed: The full analysis set (FAS) consists of all patients enrolled into the study.

Primary outcome: Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months

Time frame: Baseline, 48 weeks (12 months), 96 weeks (24 months). Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Nilotinib n = 17
Within 12 months	65 (38.3 to 85.8)
Within 24 months	71 (44.0 to 89.7)

Population analysed: The full analysis set (FAS) consists of all patients enrolled into the study. Analysis of MR4.0 was undertaken on the subgroup of the FAS that was not at MR4.0 at baseline.

Primary outcome: Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months

Time frame: Baseline, 48 weeks (12 months), 96 weeks (24 months). Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Nilotinib n = 8
Within 12 months	75 (34.9 to 96.8)
Within 24 months	75 (34.9 to 96.8)

Population analysed: The full analysis set (FAS) consists of all patients enrolled into the study.Analysis of MMR was undertaken on the subgroup of the FAS that was not at MMR at baseline.

Primary outcome: Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months

Time frame: Baseline, 96 weeks (24 months). Mean (Standard Deviation). Unit: months

Measure	Nilotinib n = 20
Achieved MR4.5	56.1 (42.06)
Did not achieve MR4.5	45.9 (47.81)

Population analysed: The full analysis set (FAS) consists of all patients enrolled into the study.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nilotinib	1 of 20 (5%)	20 of 20 (100%)	Not reported

Limitations and caveats (from the sponsor): The study was planned to enroll 130 patients. Study got terminated with 20 patients because of slow recruitment. Therefore, due to small sample size, the results cannot be considered clinical significant.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

14 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nilotinib in people with Philidelphia Positive Chronic Myeloid Leukaemia, run by Novartis Pharmaceuticals at 14 sites in Australia.

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 10 inclusion and 8 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 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Australia. 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 27 Oct 2017). 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?

Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month (time frame: Baseline, 96 weeks (24 months)). The study lists 5 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 NCT02108951.

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 27 Oct 2017.