Clinical trial NCT05024357: A Study of TKI Maintenance Therapy Following Allo-HSCT in Newly Diagnosed Ph+ Adult ALL
Official title: A Randomized Controlled Study of Tyrosine Kinase Inhibitor Maintenance Therapy Following Allogeneic Hematopoietic Stem Cell Transplantation in Newly Diagnosed Philadelphia Chromesome Positive Adult Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Philadelphia-Positive Acute Lymphoblastic Leukemia
ALL, Adult
Keywords: Philadelphia-Positive
Adult Acute Lymphoblastic Leukemia
Allogeneic Hematopoietic Stem Cell Transplantation
Tyrosine Kinase Inhibitors
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2021-08-27
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This project is a key clinical research project approved by the Clinical Research Center of the First Affiliated Hospital of Xi 'an Jiaotong University.Tyrosine kinase inhibitors (TKI) combined with chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) are routinely used in patients with philadelpha-positive lymphoblastic leukemia (Ph+ALL). However, TKI maintenance therapy post-HSCT remains controversial. In this study, Ph+ALL patients are enrolled and given dasatinib combined with chemotherapy followed by allo-HSCT. Then patients in the group A continuing to use dasatinib for 1 year is compared with those in the group B receiving dasatinib for 6 months after HSCT. The measurable residual disease (MRD), complete remission (CR), overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and the incidence of graft versus host disease (GVHD) will be observed to determine the optimal duration of TKI maintenance therapy post-HSCT.

Detailed description: About 25% of adult patients with acute lymphoblastic leukemia (ALL) are associated with t (9; 22), positive philadelphia chromosome (Ph+ ALL), in whom BCR/ABL fusion gene can be detected in the bone marrow and peripheral blood. Although current treatment strategies using tyrosine kinase inhibitors (TKIs) such as dasatinib combined with chemotherapy have achieved high complete remission (CR) rates, the duration of remission is short, and most Ph+ ALL patients relapse within 2 years. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) bridging to CR remains the only strategy to cure Ph+ ALL. However, TKI maintenance therapy post-HSCT remains controversial. In this study, Ph+ALL patients are enrolled. The participants will receive dasatinib combined with induction and consolidation chemotherapy to obtain molecular remission and then undergo allo-HSCT. After the above treatments, the patients will be randomly divided into two groups. The subjects in the group A will continue to use dasatinib for 1 year, while the patients in the group B receive dasatinib for 6 months post-HSCT. The measurable residual disease (MRD), CR, overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and the incidence of graft versus host disease (GVHD) will be observed to determine the optimal duration of TKI maintenance therapy post-HSCT.

Eligibility criteria: Inclusion Criteria:

* 18-65 years old, newly diagnosed as Ph+ALL.
* Sign the informed consent.
* Have appropriate allo-HSCT donors.
* Accept allo-HSCT.
* Accept follow-up.

Exclusion Criteria:

* Liver and kidney function impairment: serum transaminase \> 2 times of the upper limit of normal value, total bilirubin \> 1.5 times of the upper limit of normal value, serum inosine \> the upper limit of normal value (97 umol/L).
* Active hepatitis B, hepatitis C or tuberculosis infection.
* Can not tolerate the adverse effects of dasatinib.
* Pregnancy.
* Diagnosis of mental disorders.
* Failed to reach molecular complete remission (MCR) after the early treatment.
* Do not accept follow-up.

Primary outcomes:
measure: Percentage of Patients with Measurable Residual Disease (MRD) Positivity
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
measure: Percentage of Patients with Complete Remission (CR)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
Secondary outcomes:
measure: Disease-free Survival (DFS), months
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
measure: Overall Survival (OS), months
timeFrame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months.
measure: Non-relapse Mortality (NRM), rate or percentage
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
measure: Incidence of graft versus host disease (GVHD), rate or percentage
timeFrame: From date of randomization until the date of GVHD occurrence or date of death from any cause, whichever came first, assessed up to 36 months.
measure: Adverse Effects (AE)
timeFrame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months.
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xian Jiaotong University
state: Shaanxi
Study officials:
affiliation: First Affiliated Hospital of Xian Jiaotong University
name: Pengcheng He
role: STUDY_CHAIR
affiliation: First Affiliated Hospital of Xian Jiaotong University
name: Xiaoning Wang
role: STUDY_DIRECTOR
affiliation: First Affiliated Hospital of Xian Jiaotong University
name: Huachao Zhu
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Xian Jiaotong University
name: Juan Ren
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Xian Jiaotong University
name: Ying Chen
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Xian Jiaotong University
name: Ting Fan
role: PRINCIPAL_INVESTIGATOR
References: