NCT01883219

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

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

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Nanfang Hospital, Southern Medical University · Academic / Other
• Sex: All
• Age: 14 Years – 65 Years
• Healthy volunteers: Not accepted

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 description

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.

Conditions

• Philadelphia Chromosome Positive Acute Lymphocytic Leukemia
• Stem Cell Transplantation
• Minimal Residual Disease

Interventions

Type	Name	Description
DRUG	TKIs	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.

Timeline

• Start date: 2013-06-01
• Primary completion: 2016-06-01
• Completion: 2017-11-01
• First posted: 2013-06-21
• Last updated: 2017-11-08

Locations

1 site across 1 country: China