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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
Sponsor:
Collaborators:
Peking University People's Hospital
Guangxi Medical University
Guangdong Provincial People's Hospital
Guangzhou General Hospital of Guangzhou Military Command
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Third Affiliated Hospital, Sun Yat-Sen University
Information provided by (Responsible Party):
Qifa Liu, Nanfang Hospital of Southern Medical University

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).

Condition or disease Intervention/treatment Phase
Philadelphia Chromosome Positive Acute Lymphocytic Leukemia Stem Cell Transplantation Minimal Residual Disease Drug: TKIs Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
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.




Primary Outcome Measures :
  1. Overall survival(OS) [ Time Frame: 2 years ]
    OS is defined as continuous survival until death from any cause after HSCT.


Secondary Outcome Measures :
  1. Relapse rate [ Time Frame: 2 years ]
    A post-transplant relapse is defined as hematological relapse, extramedullary involvement of leukemia and cytogenetic relapse.

  2. Disease-free survival(DFS) [ Time Frame: 2 years ]
    DFS is defined as continuous survival without relapse or death from any cause after HSCT.

  3. Safety of TKI therapy [ Time Frame: 2 years ]
    The toxicity of TKI is assessed according to the Common Toxicity Criteria, version 3.0.



Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A patient age of 14-65 years
  • Allo-HSCT recipient with ph+ ALL
  • Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

  • Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
  • patients with hematological relapse, extramedullary involvement of leukemia
  • Patients with any conditions not suitable for the trial (investigators' decision)

Information from the National Library of Medicine

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


Contacts
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Contact: Ren Lin, MD +86-020-61641613 lansinglinren@hotmail.com

Locations
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China, Guangdong
Department of Hematology,Nanfang Hospital, Southern Medical University Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Ren Lin, MD    +86-020-61641613    lansinglinren@hotmail.com   
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
Peking University People's Hospital
Guangxi Medical University
Guangdong Provincial People's Hospital
Guangzhou General Hospital of Guangzhou Military Command
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Third Affiliated Hospital, Sun Yat-Sen University
Investigators
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Principal Investigator: Qifa Liu, MD Nanfang Hospital of Southern Medical University
Publications:
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Responsible Party: Qifa Liu, Professor, Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT01883219    
Other Study ID Numbers: NFEC-201304-K2
First Posted: June 21, 2013    Key Record Dates
Last Update Posted: November 8, 2017
Last Verified: June 2013
Keywords provided by Qifa Liu, Nanfang Hospital of Southern Medical University:
Philadelphia chromosome
Acute lymphoblastic leukemia
Allogeneic hematopoietic cell transplantation
Minimal residual disease
Tyrosine kinase inhibitor
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasm, Residual
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Translocation, Genetic
Chromosome Aberrations