TKI Therapy Based on Molecular Monitoring in Allogeneic-HSCT Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT01883219|
Recruitment Status : Unknown
Verified June 2013 by Qifa Liu, Nanfang Hospital of Southern Medical University.
Recruitment status was: Recruiting
First Posted : June 21, 2013
Last Update Posted : November 8, 2017
|Condition or disease||Intervention/treatment||Phase|
|Philadelphia Chromosome Positive Acute Lymphocytic Leukemia Stem Cell Transplantation Minimal Residual Disease||Drug: TKIs||Phase 2|
Philadelphia chromosome (Ph) is a reciprocal chromosomal translocation t(9;22）(q34;q11), which leads to the formation of the BCR/ABL oncogene. Ph is the most frequent cytogenetic abnormality in ALL characterized by poor outcome. With the BCR/ABL protein TKI, imatinib, in the combination chemotherapy regimes for newly diagnosed Ph+ ALL, more than 95% of patients can achieve complete remission(CR). Several studies have shown decreased relapse rates and improved disease-free survival for patients with imatinib-based treatment prior to allo-HSCT. However, the efficacy of maintenance therapy with imatinib after transplant for Ph+ ALL patients is still uncertain. In addition, acquired resistance to imatinib is frequently caused by point mutations in BCR/ABL that inactivate imatinib.
Detection of minimal residual disease (MRD) after transplant is associated with an increased risk of relapse. Reverse transcription-polymerase chain reaction (RT-PCR) is a sensitive method for detecting low-level BCR/ABL transcripts to assess MRD in Ph+ ALL. It has been corroborated by several reports that detection of MRD after SCT was predictive of imminent relapse.
In this study, we will evaluate the safety and efficacy of TKI therapy, when initiating treatment based on BCR-ABL transcript levels after allo-HSCT.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Tyrosine Kinase Inhibitor Therapy Based on Molecular Monitoring of BCR/ABL Transcript Levels in Allogeneic Hematopoietic Stem Cell Transplant Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia|
|Study Start Date :||June 2013|
|Actual Primary Completion Date :||June 2016|
|Estimated Study Completion Date :||November 2017|
Experimental: TKI therapy
Treatment with TKI will be initiated if the level of BCR-ABL transcript in the bone marrow is detectable and transcript levels increased for two consecutive tests. TKIs will be given for patients without BCR/ABL mutations and sensitive TKIs will be given for those with mutations.
Imatinib was given at a dose of 400mg/d or 600mg/d, dasatinib at a dose of 100mg/d or 140mg/d, and nilotinib at a dose of 400mg twice daily. If the patients had T315I mutations, ponatinib will be given. If the BCR/ABL levels increased or did not decrease after one month's use of TKI, donor lymphocyte infusion will be given and the TKI drugs will be modulated. If the patients experienced hematologic relapse, they will withdraw from the study.
- Overall survival(OS) [ Time Frame: 2 years ]OS is defined as continuous survival until death from any cause after HSCT.
- Relapse rate [ Time Frame: 2 years ]A post-transplant relapse is defined as hematological relapse, extramedullary involvement of leukemia and cytogenetic relapse.
- Disease-free survival(DFS) [ Time Frame: 2 years ]DFS is defined as continuous survival without relapse or death from any cause after HSCT.
- Safety of TKI therapy [ Time Frame: 2 years ]The toxicity of TKI is assessed according to the Common Toxicity Criteria, version 3.0.
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): NCT01883219
|Contact: Ren Lin, MDfirstname.lastname@example.org|
|Department of Hematology,Nanfang Hospital, Southern Medical University||Recruiting|
|Guangzhou, Guangdong, China, 510515|
|Contact: Ren Lin, MD +86-020-61641613 email@example.com|
|Principal Investigator:||Qifa Liu, MD||Nanfang Hospital of Southern Medical University|