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

Stem Cell Transplantation Clinical Trial

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

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01883219
• Other study ID #: NFEC-201304-K2
• Status: Unknown status
• Phase: Phase 2
• First received: June 14, 2013
• Last updated: November 7, 2017
• Start date: June 2013
• Est. completion date: November 2017

Study information

• Verified date: June 2013
• Source: Nanfang Hospital of Southern Medical University
• Contact: Ren Lin, MD
• Phone: +86-020-61641613
• Email: lansinglinren[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 80
• Est. completion date: November 2017
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Minimal Residual Disease
• Neoplasm, Residual
• Philadelphia Chromosome
• Philadelphia Chromosome Positive Acute Lymphocytic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Stem Cell Transplantation

Intervention

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.

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (7)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University	Guangdong Provincial People's Hospital, Guangxi Medical University, Guangzhou General Hospital of Guangzhou Military Command, Peking University People's Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Third Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (2)

Wassmann B, Pfeifer H, Stadler M, Bornhaüser M, Bug G, Scheuring UJ, Brück 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. Epub 2005 Apr 7. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival(OS)	OS is defined as continuous survival until death from any cause after HSCT.	2 years
Secondary	Relapse rate	A post-transplant relapse is defined as hematological relapse, extramedullary involvement of leukemia and cytogenetic relapse.	2 years
Secondary	Disease-free survival(DFS)	DFS is defined as continuous survival without relapse or death from any cause after HSCT.	2 years
Secondary	Safety of TKI therapy	The toxicity of TKI is assessed according to the Common Toxicity Criteria, version 3.0.	2 years