Clinical Trial: TKI Therapy Based on Molecular Monitoring in Allogeneic-HSCT Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

Study Status: Terminated
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Tyrosine Kinase Inhibitor Therapy Based on Molecular Monitoring of BCR/ABL Transcript Levels in Allogeneic Hematopoietic Stem Cell Transplant Recipients With Philadelphia Chromos

Brief Summary: The purpose of this study is to evaluate the efficacy of tyrosine kinase inhibitor(TKI) therapy based on molecular monitoring of BCR/ABL levels in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT).

Detailed Summary:

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)1. 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.


Sponsor: Nanfang Hospital of Southern Medical University

Current Primary Outcome: Disease-free survival(DFS) [ Time Frame: 2 years ]

The primary endpoint assesses the efficacy of TKI therapy. DFS is defined as continuous survival without relapse or death from any cause after HSCT.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Relapse rate [ Time Frame: 2 years ]
    A post-transplant relapse is defined as hematological relapse, extramedullary involvement of leukemia and cytogenetic relapse.
  • Overall survival(OS) [ Time Frame: 2 years ]
    OS is defined as continuous survival until 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.


Original Secondary Outcome: Same as current

Information By: Nanfang Hospital of Southern Medical University

Dates:
Date Received: June 14, 2013
Date Started: June 2013
Date Completion: June 2016
Last Updated: June 23, 2013
Last Verified: June 2013