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

NCT01883219 | Unknown Phase 2 DMC

• 1 other identifier: NFEC-201304-K2
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

Primary Outcomes (1)

• Overall survival(OS)

  OS is defined as continuous survival until death from any cause after HSCT.

  2 years

Secondary Outcomes (3)

• Relapse rate

  2 years

• Disease-free survival(DFS)

  2 years

• Safety of TKI therapy

  2 years

Study Arms (1)

TKI therapy

EXPERIMENTAL

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

Interventions

TKIs DRUG

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.

TKI therapy

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• Peking University People's Hospital: collaborator
• Guangxi Medical University: collaborator
• Guangdong Provincial People's Hospital: collaborator
• Guangzhou General Hospital of Guangzhou Military Command: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator

Study Sites (1)

Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

Related Publications (3)

• 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.

  PMID: 18986386 BACKGROUND

• 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.

  PMID: 15817679 BACKGROUND

• 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.

  PMID: 33204013 DERIVED

MeSH Terms

Conditions

Neoplasm, Residual; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Translocation, Genetic; Chromosome Aberrations; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Qifa Liu, MD

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ren Lin, MD

CONTACT

+86-020-61641613; lansinglinren@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: June 21, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: November 1, 2017
• Last Updated: November 8, 2017

Record last verified: 2013-06

Locations

CN (1)