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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02108951




Registration number
NCT02108951
Ethics application status
Date submitted
7/04/2014
Date registered
9/04/2014
Date last updated
27/10/2017

Titles & IDs
Public title
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.
Scientific 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).
Secondary ID [1] 0 0
CAMN107AAU04
Universal Trial Number (UTN)
Trial acronym
ENESTswift
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Philidelphia Positive Chronic Myeloid Leukaemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nilotinib

Experimental: Nilotinib - 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.


Treatment: Drugs: Nilotinib
Nilotinib 150mg hard gelatin capsules taken orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month
Timepoint [1] 0 0
Baseline, 96 weeks (24 months)
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Baseline, 48 weeks (12 months), 96 weeks (24 months)
Primary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline, 48 weeks (12 months), 96 weeks (24 months)
Primary outcome [4] 0 0
Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months
Timepoint [4] 0 0
Baseline, 96 weeks (24 months)
Primary outcome [5] 0 0
Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
Timepoint [5] 0 0
Baseline, 96 weeks (24 months)
Secondary outcome [1] 0 0
Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Timepoint [1] 0 0
Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Secondary outcome [2] 0 0
Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Timepoint [2] 0 0
Baseline, week 4, 8, 12, 24, 36, 48, 60, 72 and 96
Secondary outcome [3] 0 0
Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Timepoint [3] 0 0
Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Secondary outcome [4] 0 0
Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Timepoint [4] 0 0
Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Secondary outcome [5] 0 0
Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5)
Timepoint [5] 0 0
96 weeks (24 months)
Secondary outcome [6] 0 0
Time to Progression-free Survival (PFS)
Timepoint [6] 0 0
96 weeks (24 months)
Secondary outcome [7] 0 0
Time to Event Free Survival (EFS)
Timepoint [7] 0 0
96 weeks (24 months)
Secondary outcome [8] 0 0
Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit
Timepoint [8] 0 0
Baseline, week 12 (month 3)
Secondary outcome [9] 0 0
Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Timepoint [9] 0 0
Baseline, week 12, 24, 48, 96

Eligibility
Key inclusion criteria
1. Written informed consent prior to screening procedures
2. Eastern Cooperative Oncology Grou (ECOG) Performance Status of 0, 1, or 2.
3. Patient with diagnosis of Ph+ CML-CP associated with BCR-ABL quantifiable by RQ-PCR (IS).
4. Patient has received a minimum of 3 months of imatinib or dasatinib treatment (any dose) since initial diagnosis with a documented response.
5. Patient is eligible for Pharmaceutical Benefits Scheme (PBS) reimbursed 1st line TKI treatment.
6. 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.
7. No other current or planned anti-leukemia therapies.
8. Adequate organ function.
9. Potassium, Magnesium and Total Calcium above Lower limit of normal.
10. life expectancy of more than 12 months in the absence of any intervention

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior treatment with nilotinib.
2. 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).
3. Patient has documented Molecular Response (MR) 4.5 at the time of study entry
4. Patients with atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.
5. Known impaired cardiac function.
6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
7. Pregnant or breast feeding (lactating) women.
8. Women of child-bearing potential unwilling or unable to use highly effective contraception.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/07/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/08/2016
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Canberra
Recruitment hospital [2] 0 0
Novartis Investigative Site - Kingswood
Recruitment hospital [3] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [4] 0 0
Novartis Investigative Site - Liverpool
Recruitment hospital [5] 0 0
Novartis Investigative Site - St. Leonards
Recruitment hospital [6] 0 0
Novartis Investigative Site - Douglas
Recruitment hospital [7] 0 0
Novartis Investigative Site - Nambour
Recruitment hospital [8] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [9] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [10] 0 0
Novartis Investigative Site - Fitzroy
Recruitment hospital [11] 0 0
Novartis Investigative Site - Geelong
Recruitment hospital [12] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [13] 0 0
Novartis Investigative Site - Murdoch
Recruitment hospital [14] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
2747 - Kingswood
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2065 - St. Leonards
Recruitment postcode(s) [6] 0 0
4810 - Douglas
Recruitment postcode(s) [7] 0 0
4560 - Nambour
Recruitment postcode(s) [8] 0 0
4101 - South Brisbane
Recruitment postcode(s) [9] 0 0
5000 - Adelaide
Recruitment postcode(s) [10] 0 0
3065 - Fitzroy
Recruitment postcode(s) [11] 0 0
3220 - Geelong
Recruitment postcode(s) [12] 0 0
3000 - Melbourne
Recruitment postcode(s) [13] 0 0
6150 - Murdoch
Recruitment postcode(s) [14] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02108951
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02108951