Prospective Investigation of Dynamics of ABL Mutations in Imatinib Failed CML Patients Treated With Nilotinib (AMICAN)
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|ClinicalTrials.gov Identifier: NCT01562847|
Recruitment Status : Unknown
Verified January 2014 by Dong-Wook Kim, Seoul St. Mary's Hospital.
Recruitment status was: Active, not recruiting
First Posted : March 26, 2012
Last Update Posted : January 13, 2014
|Condition or disease||Intervention/treatment|
|Chronic Myeloid Leukemia||Drug: Nilotinib|
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 Type :||Observational|
|Estimated Enrollment :||125 participants|
|Observational Model:||Case Control|
|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|
|Study Start Date :||July 2011|
|Estimated Primary Completion Date :||June 2014|
|Estimated Study Completion Date :||June 2015|
Patients will be treated with 800 mg nilotinib daily.
Other Name: Nilotinib: Tasigna
- To confirm the patterns of resistance including point mutations which are newly expressed during the nilotinib treatment [ Time Frame: 5 years ]
- 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 ]
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01562847
|Korea, Republic of|
|Seoul St. Mary's Hospital|
|Seoul, Korea, Republic of, 137-701|
|Principal Investigator:||Dong-Wook Kim, MD, PhD||Seoul St. Mary's Hospital|