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

NCT ID: NCT01883219

Last Updated: 2017-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2017-11-30

Brief Summary

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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

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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

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

Keywords

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Philadelphia chromosome Acute lymphoblastic leukemia Allogeneic hematopoietic cell transplantation Minimal residual disease Tyrosine kinase inhibitor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

TKIs

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

14 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University People's Hospital

OTHER

Sponsor Role collaborator

Guangxi Medical University

OTHER

Sponsor Role collaborator

Guangdong Provincial People's Hospital

OTHER

Sponsor Role collaborator

Guangzhou General Hospital of Guangzhou Military Command

OTHER

Sponsor Role collaborator

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role collaborator

Third Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role lead

Responsible Party

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Qifa Liu

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Qifa Liu, MD

Role: PRINCIPAL_INVESTIGATOR

Nanfang Hospital, Southern Medical University

Locations

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Department of Hematology,Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Ren Lin, MD

Role: CONTACT

Phone: +86-020-61641613

Email: [email protected]

Facility Contacts

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Ren Lin, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 18986386 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15817679 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33204013 (View on PubMed)

Other Identifiers

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NFEC-201304-K2

Identifier Type: -

Identifier Source: org_study_id