Clinical trial NCT01883219: TKI Therapy Based on Molecular Monitoring in Allogeneic-HSCT Recipients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Philadelphia Chromosome Positive Acute Lymphocytic Leukemia
Stem Cell Transplantation
Minimal Residual Disease
Keywords: Philadelphia chromosome
Acute lymphoblastic leukemia
Allogeneic hematopoietic cell transplantation
Minimal residual disease
Tyrosine kinase inhibitor
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Peking University People's Hospital
name: Guangxi Medical University
name: Guangdong Provincial People's Hospital
name: Guangzhou General Hospital of Guangzhou Military Command
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Third Affiliated Hospital, Sun Yat-Sen University
First posted: 2013-06-21
Enrollment: 80
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.

Eligibility 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)

Primary outcomes:
measure: Overall survival(OS)
timeFrame: 2 years
Secondary outcomes:
measure: Relapse rate
timeFrame: 2 years
measure: Disease-free survival(DFS)
timeFrame: 2 years
measure: Safety of TKI therapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Qifa Liu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yanada M, Sugiura I, Takeuchi J, Akiyama H, Maruta A, Ueda Y, Usui N, Yagasaki F, Yujiri T, Takeuchi M, Nishii K, Kimura Y, Miyawaki S, Narimatsu H, Miyazaki Y, Ohtake S, Jinnai I, Matsuo K, Naoe T, Ohno R; Japan Adult Leukemia Study Group. Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy. Br J Haematol. 2008 Nov;143(4):503-10. doi: 10.1111/j.1365-2141.2008.07377.x.
citation: Wassmann B, Pfeifer H, Stadler M, Bornhauser M, Bug G, Scheuring UJ, Bruck P, Stelljes M, Schwerdtfeger R, Basara N, Perz J, Bunjes D, Ledderose G, Mahlberg R, Binckebanck A, Gschaidmeier H, Hoelzer D, Ottmann OG. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2005 Jul 15;106(2):458-63. doi: 10.1182/blood-2004-05-1746. Epub 2005 Apr 7.
citation: Liu H, Xuan L, Lin R, Deng L, Fan Z, Nie D, Li X, Liang X, Xu D, Zhang Y, Xu N, Ye J, Jin H, Lin D, Ma L, Sun J, Huang F, Liu Q. A new pre-emptive TKIs strategy for preventing relapse based on BCR/ABL monitoring for Ph+ALL undergoing allo-HCT: a prospective clinical cohort study. Leukemia. 2021 Jul;35(7):2054-2063. doi: 10.1038/s41375-020-01090-4. Epub 2020 Nov 17.