Myeloid Leukemia, ChronicPhase 4NISRINCT02086487
Efficacy and Safety Assessment of NIlotinib in CML Patients With Suboptimal Response on Imatinib Therapy
A Phase 4 study testing Nilotinib 300 mg. in people with Myeloid Leukemia, Chronic, run by King Abdullah International Medical Research Center at 2 sites in Saudi Arabia.
Trial summary
whether Nilotinib at the two sequential dosage forms will induce quicker and deeper response in those patients, and if FISH on PB (Peripheral blood) would be an effective way to monitor response compared to conventional cytogenetics on bone marrow (BM) sample Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Myeloid Leukemia, Chronic
- What is being tested?
- Nilotinib 300 mg.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 2 sitesSaudi Arabia
- Study dates
- Mar 2013to Aug 2016
- Phase
- Phase 4
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent prior to any study procedures being performed.
- Age 18 or above of male or female CML patients in chronic phase.
- Eastern Cooperative Oncology Group ECOG Performance status 0, 1 or 2
- Sub-optimal response on Imatinib therapy as determined by any of the following criteria: 4.1) Minor cytogenetic response mCyR or minimal response at 3 months (Ph+ metaphases in BM 35 to 95 %) 4.2) BCR-ABL1 transcript >10% at 3 months; 4.3) Partial cytogenetic response PCyR at 6 months; (i.e Ph+ metaphases in BM 0 to 35%) 4.4) BCR-ABL1 transcript 1 - 10% at 6 months 4.5) Less than a major molecular response at > 12 months; i.e (BCR-ABL1 0.1 - 1%)
- Normal serum levels of potassium, magnesium and calcium ≥ LLN (lower limit of normal) or corrected to within normal limits with supplements, prior to the first dose of study medication,
- Aspartate aminotransferase AST and Alanine aminotransferase ALT ≤ 2.5 x ULN (upper limit of normal)
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- Alkaline phosphatase ≥ 2.5 x ULN
- Total bilirubin ≤ 1.5 x ULN;
- Serum amylase ≤ 1.5 x ULN Performance status ECOG 0,1,2
Who cannot join
- Previous Exposure to Tyrosine Kinase Inhibitor (TKI) other than Imatinib for more than 2 weeks
- Patients who are already participating in any other clinical trial.Patients who were not compliant to Imatinib therapy.
- Optimal response to Imatinib therapy as determined by any one of the criteria: 3.1. CCyR or PCyR at 3 months (Ph+ metaphases in BM ≤ 35 %). 3.2. BCR-ABL1 transcript ≤ 10 % at 3 months. 3.3. CCyR at 6 months (Ph+ metaphases in BM 0 %). 3.4. BCR-ABL1 transcript < 1% at 6 months. 3.5. BCR-ABL1 transcript ≤ 0.1 % at 12 months. 3.6. BCR-ABL1 transcript ≤ 0.1 % at any time.
- Failure response to Imatinib therapy as per ELN guidelines 2013 as determined by any of the criteria: 4.1. Non- complete hematologic response (Non- CHR) or no cytogenetic response CyR at 3 months (Ph+ metaphases in BM > 95 %). 4.2. Less than Partial cytogenetic response PCyR at 6 months (Ph+ metaphases in BM > 35%). 4.3. BCR-ABL1 transcript >10 % at 6 months. 4.4. Less than complete cytogenetic response CCyR at 12 months (Ph+ metaphases in BM > 0 %). 4.5. BCR-ABL1 transcript >1 % at 12 months. 4.6. Loss of CHR or loss of CCyR or confirmed loss of MMR* or development of partially imatinib - sensitive BCR-ABL mutation or CCA in Ph- positive cells at any time.
- Pregnant or lactating females
- Patients with prolonged QT intervals
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- Patient with history of pancreatitis
- Previously documented T315I mutations;
- Uncontrolled congestive heart failure or hypertension;
- Myocardial infarction or unstable angina pectoris within past 12 months;
- Significant arrhythmias, including history or presence of clinically significant ventricular or atrial tachyarrhythmias, clinically -significant bradycardias, long QT syndrome and/or corrected QT interval (QTc) > 450 msec on screening ECG. Patients with complete LBBB (Left Bundle Branch Block);
- Patients concurrently on strong CYP3A4 inhibitors.
- Other concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol;
- Impaired gastrointestinal function or GI disease that may alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery);
- Patients with another primary malignancy that is currently clinically significant or requires active intervention.
Trial locations and contacts
2 sites in 1 country.
Saudi Arabia2 sites
King Fahad specialist Hospital
Dammam, Eastern Province
National Guard Hospital
Riyadh, Central, 11426
About this study
Official title: Efficacy and Safety Assessment of NIlotinib in CML Patients With Suboptimal Response on Imatinib Therapy (NISRI)
whether Nilotinib at the two sequential dosage forms will induce quicker and deeper response in those patients, and if FISH on PB (Peripheral blood) would be an effective way to monitor response compared to conventional cytogenetics on bone marrow (BM) sample
Read the detailed description
This is a multicenter, open label trial which will be conducted within Kingdom of saudi Arabia for which CML (Chronic Myeloid Leukemia) patients who meet eligibility criteria and showing sub optimal response to Imatinib therapy as per European leukemia Net ELN 2013 guidelines will be recruited and switched to Nilotinib 300 mg twice a day therapy.
Efficacy assessments of hematologic and cytogenetic response and disease progression, will be performed every 6 months at a minimum, including hematologic analysis, bone marrow cytogenetics, and molecular studies to ensure that nilotinib is being provided to patients who were responding and that patients who progressed could discontinue therapy.
Safety assessments include evaluation of adverse events, hematologic assessment, biochemical testing, cardiac enzyme assessment, serial electrocardiogram evaluation, and physical examination. Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Survival will be dated from start of nilotinib therapy until death from any cause and censored at last follow-up for patients who were alive.
The data will be summarized with respect to demographic and baseline characteristics, efficacy evaluation, and safety observations and measurements.
- Conditions
- Myeloid Leukemia, Chronic
- Being tested
- Nilotinib 300 mg.
- Keywords
- NIlotinib , Suboptimal Response , Imatinib
- 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.
Nilotinib 300 mg.Drug
Also called Tasigna 300 mg
Patients diagnosed with chronic myeloid leukemia receiving treatment of Imatinib 400 mg once a day but are determined to be sub-optimally responding to Imatinib therapy as per the ELN 2013 guidelines will be switched to Nilotinib 300 mg BID and then will be assessed for therapy response. ELN guidelines 2013 for imatinib therapy response states as:
Minor cytogenetic response mCyR or minimal response at 3 months (Ph+ metaphases in BM 35 to 95 %); BCR-ABL1 transcript > 10% at 3 months; Partial cytogenetic response at 6 months Ph+ metaphases in BM 0to 35); BCR-ABL1 transcript is 1 to 10% at 6 months. Less than a major molecular response at > 12 months; i.e (BCR-ABL1 0.1 -1%)
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib 300 mg | Experimental | Patients diagnosed with chronic myeloid leukemia receiving treatment of Imatinib 400 mg but show sub-optimal response on Imatinib therapy as per the ELN 2013 guidelines will be switched to Nilotinib 300 mg twice daily and will be assessed for timely.
In the absence of safety concerns, nilotinib could be escalated to 400 mg twice daily if patients had not obtained any of the following milestones:
1. BCR-ABL1 transcript level ≤ 10% at 3 months;
2. CCyR at 6 months,
3. BCR/ABL1 ≤ 1% at 6 months
4. MMR at 12 months, or
5. if they showed loss of cytogenetic or molecular response or disease progression at any time. Failure and thus, stopping nilotinib will be considered if any of above milestones happened while on the 400mg twice daily dose. Receives: Drug: Nilotinib 300 mg. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary efficacy variable of this study is the overall Major molecular response at 12 month after starting Nilotinib 300mg twice daily for patient who suboptimally responded to Imatinib as per the ELN guidelines
Measured: 12 Months
Secondary outcomes (6)
Rate of cytogenetic response (complete cytogenetic response CCyR and Major cytogenetic response MCyR) and Major molecular response MMR at 3, 6 and 12 months of starting Nilotinib in patients who had a suboptimal response on Imatinib.
Measured: 12Months
Rate of CCyR at 6 months and MMR at 6 and 12 months from Nilotinib dose escalating to 400 mg BID.
Measured: 12 months
Rate and duration of Complete Hematologic Response CHR.
Measured: 12 months
Rate of CMR at 12 months of Nilotinib.
Measured: 12 months
Comparison of FISH results with conventional cytogenetics at 3, 6 & 12 months.
Measured: 12
Overall survival.
Measured: 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2014 (estimated)
- Study startMar 2013
- Primary completionAug 2016
- Study completionAug 2016
Why it stopped: Because of many unseen obstacles resulted in poor accrual, study is terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myeloid Leukemia, ChronicStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- King Abdullah International Medical Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Dr. Ahmad S. Alaskar, MD,FACP,FRCP, Principal investigator, King Abdulaziz Medical City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02086487
- Sponsor's protocol ID
- RC12/052
- Acronym
- NISRI
- Status last verified
- Mar 2017
- First submitted
- 27 Feb 2014
- Last updated
- 7 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety Assessment of NIlotinib in CML Patients With Suboptimal Response on Imatinib Therapy (NISRI)
- ClinicalTrials.gov ID
- NCT02086487
- Acronym / sponsor ID
- NISRI / RC12/052
- Conditions
- Myeloid Leukemia, Chronic
- Keywords
- NIlotinib , Suboptimal Response , Imatinib
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Because of many unseen obstacles resulted in poor accrual, study is terminated.
- Enrolment
- 98 participants (actual)
- Lead sponsor
- King Abdullah International Medical Research CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Mar 2013
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 13 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
whether Nilotinib at the two sequential dosage forms will induce quicker and deeper response in those patients, and if FISH on PB (Peripheral blood) would be an effective way to monitor response compared to conventional cytogenetics on bone marrow (BM) sample
Detailed description
This is a multicenter, open label trial which will be conducted within Kingdom of saudi Arabia for which CML (Chronic Myeloid Leukemia) patients who meet eligibility criteria and showing sub optimal response to Imatinib therapy as per European leukemia Net ELN 2013 guidelines will be recruited and switched to Nilotinib 300 mg twice a day therapy.
Efficacy assessments of hematologic and cytogenetic response and disease progression, will be performed every 6 months at a minimum, including hematologic analysis, bone marrow cytogenetics, and molecular studies to ensure that nilotinib is being provided to patients who were responding and that patients who progressed could discontinue therapy.
Safety assessments include evaluation of adverse events, hematologic assessment, biochemical testing, cardiac enzyme assessment, serial electrocardiogram evaluation, and physical examination. Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Survival will be dated from start of nilotinib therapy until death from any cause and censored at last follow-up for patients who were alive.
The data will be summarized with respect to demographic and baseline characteristics, efficacy evaluation, and safety observations and measurements.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib 300 mg | Experimental | Drug: Nilotinib 300 mg.Patients diagnosed with chronic myeloid leukemia receiving treatment of Imatinib 400 mg but show sub-optimal response on Imatinib therapy as per the ELN 2013 guidelines will be switched to Nilotinib 300 mg twice daily and will be assessed for timely. In the absence of safety concerns, nilotinib could be escalated to 400 mg twice daily if patients had not obtained any of the following milestones: 1. BCR-ABL1 transcript level ≤ 10% at 3 months; 2. CCyR at 6 months, 3. BCR/ABL1 ≤ 1% at 6 months 4. MMR at 12 months, or 5. if they showed loss of cytogenetic or molecular response or disease progression at any time. Failure and thus, stopping nilotinib will be considered if any of above milestones happened while on the 400mg twice daily dose. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Written informed consent prior to any study procedures being performed.
- Age 18 or above of male or female CML patients in chronic phase.
- Eastern Cooperative Oncology Group ECOG Performance status 0, 1 or 2
- Sub-optimal response on Imatinib therapy as determined by any of the following criteria: 4.1) Minor cytogenetic response mCyR or minimal response at 3 months (Ph+ metaphases in BM 35 to 95 %) 4.2) BCR-ABL1 transcript >10% at 3 months; 4.3) Partial cytogenetic response PCyR at 6 months; (i.e Ph+ metaphases in BM 0 to 35%) 4.4) BCR-ABL1 transcript 1 - 10% at 6 months 4.5) Less than a major molecular response at > 12 months; i.e (BCR-ABL1 0.1 - 1%)
- Normal serum levels of potassium, magnesium and calcium ≥ LLN (lower limit of normal) or corrected to within normal limits with supplements, prior to the first dose of study medication,
Key exclusion criteria (15 listed)
- Previous Exposure to Tyrosine Kinase Inhibitor (TKI) other than Imatinib for more than 2 weeks
- Patients who are already participating in any other clinical trial.Patients who were not compliant to Imatinib therapy.
- Optimal response to Imatinib therapy as determined by any one of the criteria: 3.1. CCyR or PCyR at 3 months (Ph+ metaphases in BM ≤ 35 %). 3.2. BCR-ABL1 transcript ≤ 10 % at 3 months. 3.3. CCyR at 6 months (Ph+ metaphases in BM 0 %). 3.4. BCR-ABL1 transcript < 1% at 6 months. 3.5. BCR-ABL1 transcript ≤ 0.1 % at 12 months. 3.6. BCR-ABL1 transcript ≤ 0.1 % at any time.
- Failure response to Imatinib therapy as per ELN guidelines 2013 as determined by any of the criteria: 4.1. Non- complete hematologic response (Non- CHR) or no cytogenetic response CyR at 3 months (Ph+ metaphases in BM > 95 %). 4.2. Less than Partial cytogenetic response PCyR at 6 months (Ph+ metaphases in BM > 35%). 4.3. BCR-ABL1 transcript >10 % at 6 months. 4.4. Less than complete cytogenetic response CCyR at 12 months (Ph+ metaphases in BM > 0 %). 4.5. BCR-ABL1 transcript >1 % at 12 months. 4.6. Loss of CHR or loss of CCyR or confirmed loss of MMR* or development of partially imatinib - sensitive BCR-ABL mutation or CCA in Ph- positive cells at any time.
- Pregnant or lactating females
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 |
|---|---|---|
| Nilotinib 300 mg.Also: Tasigna 300 mgPatients diagnosed with chronic myeloid leukemia receiving treatment of Imatinib 400 mg once a day but are determined to be sub-optimally responding to Imatinib therapy as per the ELN 2013 guidelines will be switched to Nilotinib 300 mg BID and then will be assessed for therapy response. ELN guidelines 2013 for imatinib therapy response states as: Minor cytogenetic response mCyR or minimal response at 3 months (Ph+ metaphases in BM 35 to 95 %); BCR-ABL1 transcript > 10% at 3 months; Partial cytogenetic response at 6 months Ph+ metaphases in BM 0to 35); BCR-ABL1 transcript is 1 to 10% at 6 months. Less than a major molecular response at > 12 months; i.e (BCR-ABL1 0.1 -1%) | Drug | Nilotinib 300 mg |
Primary outcome
The primary efficacy variable of this study is the overall Major molecular response at 12 month after starting Nilotinib 300mg twice daily for patient who suboptimally responded to Imatinib as per the ELN guidelines
Time frame: 12 Months
6 secondary outcomes
Rate of cytogenetic response (complete cytogenetic response CCyR and Major cytogenetic response MCyR) and Major molecular response MMR at 3, 6 and 12 months of starting Nilotinib in patients who had a suboptimal response on Imatinib.
Time frame: 12Months
Rate of CCyR at 6 months and MMR at 6 and 12 months from Nilotinib dose escalating to 400 mg BID.
Time frame: 12 months
Rate and duration of Complete Hematologic Response CHR.
Time frame: 12 months
Rate of CMR at 12 months of Nilotinib.
Time frame: 12 months
Comparison of FISH results with conventional cytogenetics at 3, 6 & 12 months.
Time frame: 12
Overall survival.
Time frame: 12
Results and safety
The study was stopped early (reason given: Because of many unseen obstacles resulted in poor accrual, study is terminated.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
- Individual participant dataSharing planned: Undecided
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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.
Dr. Ahmad S. Alaskar, MD,FACP,FRCP principal investigator
King Abdulaziz Medical City
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nilotinib 300 mg. in people with Myeloid Leukemia, Chronic, run by King Abdullah International Medical Research Center at 2 sites in Saudi Arabia.
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 9 inclusion and 15 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 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Saudi Arabia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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: Because of many unseen obstacles resulted in poor accrual, study is terminated.). 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?
The primary efficacy variable of this study is the overall Major molecular response at 12 month after starting Nilotinib 300mg twice daily for patient who suboptimally responded to Imatinib as per the ELN guidelines (time frame: 12 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Mar 2017.