Chronic Myeloid LeukemiaAMICANNCT01562847
Prospective Investigation of Dynamics of ABL Mutations in Imatinib Failed CML Patients Treated With Nilotinib
An observational study of Chronic Myeloid Leukemia, run by Seoul St. Mary's Hospital at 1 site in South Korea.
Trial summary
The purposes of this study are to investigate expression and frequency of ABL point mutations, a major cause of resistance in imatinib failed CML Asian patients and to find causes of Asian-specific resistance to cancer-targeting therapies through a prospective investigation of dynamics of point mutations and… 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?
- Nilotinib
- How many people
- 125 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jul 2011to Jun 2015
- Phase
- Observational
- 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
Study population: Korean Adult CML patients
Who may be able to join
- Patients with Philadelphia chromosome-positive or BCR-ABL positive CML
- Chronic, Accelerated phase CML patients who show an inappropriate response to the imatinib treatment or failed the treatment according to ELN 2009 RECOMMENDATION
- Patients with ECOG performance status of 0-3
- Patients who consent to the use of study information and study specimen
Who cannot join
- Patients with diseases other than CML
- Patients treated with myelosuppressive anticancer therapy other than Hydroxyurea and Angrelide
- Patients who have been treated with second-generation cancer-targeting drug
- Patients who do not consent to the use of study information and study specimen
- Previously documented T315I mutation
- Impaired cardiac function including any of the following: LVEF by echocardiography < 45% or below the institutional lower range (whichever is greater); complete left bundle branch block; long QT syndrome or family history of; history or presence of significant ventricular or atrial tachyarrhythmias; clinically significant brachycardia (< 50 bpm); QTcF > 450 msec at baseline; right bundle branch block plus left anterior hemiblock; bifascicular block; myocardial infarction ≤ 12 months; uncontrolled angina; other clinically significant heart disease (e.g., congestive heart failure)
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- Treatment with strong inhibitors of CYP3A4 or medication that are well documented to prolong the QT interval are contraindicated
- Impaired gastrointestinal(GI)function or GI disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomitting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery)
- History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- Know cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required)
- Patients who previously had a bone marrow or stem cell transplantation
- Pregnant or breast-feeding patients
- Hypersensitivity to nilotinib or any of the excipients
- The capsules contain lactose, and nilotinib is therefore not recommended for patients with rare hereditary problem of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dynamics of ABL Mutations in Imatinib Failed Ph Positive or Bcr-Abl Positive CML CP or AP Patients Who Treated With Nilotinib as Second-line TKI Therapy (AMICAN-Prospective)in Asia
The purposes of this study are to investigate expression and frequency of ABL point mutations, a major cause of resistance in imatinib failed CML Asian patients and to find causes of Asian-specific resistance to cancer-targeting therapies through a prospective investigation of dynamics of point mutations and expression of new point mutations during nilotinib treatment.
Read the detailed description
Recently the treatment strategy of Philadelphia chromosome-positive leukemia has undergone groundbreaking changes due to the development of new second-generation cancer-targeting drugs. After 2001, a seven-year survival for leukemia stands at as much as 86 percent due to the oral therapy of cancer-targeting imatinib as a standard treatment, but drug resistance occurs in some patients in the early stage of the treatment. It is known that weakened binding ability of imatinib to BCR-ABL is due to a point mutation in the ATP-binding site of BCR-ABL. This accounts for 70 percent of causes of imatinib resistance. According to the studies so far, there are approximately more than 60 types of BCR-ABL point mutation, which causes imatinib resistance.
The international phase II clinical study of dasatinib and nilotinib, second-generation cancer-targeting therapies, in imatinib failed patients which began in 2005 showed that more than 70 percent of the patients achieved a complete hematological response (CHR) again, and about 50 percent of the patients, a major hematological response (MHR). In the study, it was also observed that kinase activation was inhibited by a second-generation cancer-targeting therapy for most of the major imatinib-resistant point mutations. With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. T315I mutation exhibits strong resistance to both of these cancer-targeting therapies. Therefore, it is considered that the second-generation cancer-targeting therapies show therapeutic effects in different domains.
According to the results of the recent studies including the one conducted by our center, it is assumed that imatinib resistance caused by point mutations in patients induces more point mutations and causes selective increase in T315I point mutations during treatment of the second-generation cancer-targeting therapy.
However, in the studies so far, the subjects were selectively chosen in advance for the pharmaceutical company to receive an approval from the health authorities and ABL point mutations were followed up during the limited study period, which indicates that there have been limits to accurately observe and evaluate dynamics of point mutations throughout treatment with the second-generation cancer-targeting drug.
For this reason, this study is designed to examine ABL point mutations in patients with Philadelphia chromosome-positive or BCR-ABL-positive chronic leukemia who are treated with imatinib, to observe dynamics of existing point mutations during treatment with nilotinib, and to confirm the mechanism of resistance including expression of new point mutations and their expression patterns through a long-term follow-up. In addition, this study will confirm whether expression pattern of ABL point mutations associated with nilotinib in Asian is different from that in Western patients.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- 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.
NilotinibDrug
Also called Nilotinib: Tasigna
Patients will be treated with 800 mg nilotinib daily.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Not described Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To confirm the patterns of resistance including point mutations which are newly expressed during the nilotinib treatment
Measured: 5 years
Secondary outcomes (1)
To analyze and evaluate the overall survival and disease free survival in the nilotinib treatment according to progression of the disease and types of point mutations
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2012 (estimated)
- Study startJul 2011
- Primary completionJun 2014 (estimated)
- Study completionJun 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul St. Mary's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, Dong-Wook Kim, Seoul St. Mary's Hospital
- Investigators
- Dong-Wook Kim, MD, PhD, Principal investigator, Seoul St. Mary's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01562847
- Sponsor's protocol ID
- CAMN107AKR05T
- Acronym
- AMICAN
- Status last verified
- Jan 2014
- First submitted
- 21 Jul 2011
- Last updated
- 13 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamics of ABL Mutations in Imatinib Failed Ph Positive or Bcr-Abl Positive CML CP or AP Patients Who Treated With Nilotinib as Second-line TKI Therapy (AMICAN-Prospective)in Asia
- ClinicalTrials.gov ID
- NCT01562847
- Acronym / sponsor ID
- AMICAN / CAMN107AKR05T
- Conditions
- Chronic Myeloid Leukemia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- Seoul St. Mary's HospitalUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jul 2011
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Jun 2015 (estimated)
- First posted
- 26 Mar 2012 (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.
The purposes of this study are to investigate expression and frequency of ABL point mutations, a major cause of resistance in imatinib failed CML Asian patients and to find causes of Asian-specific resistance to cancer-targeting therapies through a prospective investigation of dynamics of point mutations and expression of new point mutations during nilotinib treatment.
Detailed description
Recently the treatment strategy of Philadelphia chromosome-positive leukemia has undergone groundbreaking changes due to the development of new second-generation cancer-targeting drugs. After 2001, a seven-year survival for leukemia stands at as much as 86 percent due to the oral therapy of cancer-targeting imatinib as a standard treatment, but drug resistance occurs in some patients in the early stage of the treatment. It is known that weakened binding ability of imatinib to BCR-ABL is due to a point mutation in the ATP-binding site of BCR-ABL. This accounts for 70 percent of causes of imatinib resistance. According to the studies so far, there are approximately more than 60 types of BCR-ABL point mutation, which causes imatinib resistance.
The international phase II clinical study of dasatinib and nilotinib, second-generation cancer-targeting therapies, in imatinib failed patients which began in 2005 showed that more than 70 percent of the patients achieved a complete hematological response (CHR) again, and about 50 percent of the patients, a major hematological response (MHR). In the study, it was also observed that kinase activation was inhibited by a second-generation cancer-targeting therapy for most of the major imatinib-resistant point mutations. With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. T315I mutation exhibits strong resistance to both of these cancer-targeting therapies. Therefore, it is considered that the second-generation cancer-targeting therapies show therapeutic effects in different domains.
According to the results of the recent studies including the one conducted by our center, it is assumed that imatinib resistance caused by point mutations in patients induces more point mutations and causes selective increase in T315I point mutations during treatment of the second-generation cancer-targeting therapy.
However, in the studies so far, the subjects were selectively chosen in advance for the pharmaceutical company to receive an approval from the health authorities and ABL point mutations were followed up during the limited study period, which indicates that there have been limits to accurately observe and evaluate dynamics of point mutations throughout treatment with the second-generation cancer-targeting drug.
For this reason, this study is designed to examine ABL point mutations in patients with Philadelphia chromosome-positive or BCR-ABL-positive chronic leukemia who are treated with imatinib, to observe dynamics of existing point mutations during treatment with nilotinib, and to confirm the mechanism of resistance including expression of new point mutations and their expression patterns through a long-term follow-up. In addition, this study will confirm whether expression pattern of ABL point mutations associated with nilotinib in Asian is different from that in Western patients.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | – | Drug: Nilotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Korean Adult CML patients
Key inclusion criteria (4 listed)
- Patients with Philadelphia chromosome-positive or BCR-ABL positive CML
- Chronic, Accelerated phase CML patients who show an inappropriate response to the imatinib treatment or failed the treatment according to ELN 2009 RECOMMENDATION
- Patients with ECOG performance status of 0-3
- Patients who consent to the use of study information and study specimen
Key exclusion criteria (14 listed)
- Patients with diseases other than CML
- Patients treated with myelosuppressive anticancer therapy other than Hydroxyurea and Angrelide
- Patients who have been treated with second-generation cancer-targeting drug
- Patients who do not consent to the use of study information and study specimen
- Previously documented T315I mutation
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: Nilotinib: TasignaPatients will be treated with 800 mg nilotinib daily. | Drug | Nilotinib |
Primary outcome
To confirm the patterns of resistance including point mutations which are newly expressed during the nilotinib treatment
Time frame: 5 years
1 secondary outcome
To analyze and evaluate the overall survival and disease free survival in the nilotinib treatment according to progression of the disease and types of point mutations
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2014.
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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.
Dong-Wook Kim, MD, PhD principal investigator
Seoul St. Mary's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Myeloid Leukemia, run by Seoul St. Mary's Hospital at 1 site in South Korea.
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 4 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 13 Jan 2014. 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 South Korea. 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.
Are results available for this study?
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?
To confirm the patterns of resistance including point mutations which are newly expressed during the nilotinib treatment (time frame: 5 years). 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 13 Jan 2014.