Clinical trial NCT05026229: A Study of Dasatinib Plus Reduced Intensive Consolidation Chemotherapy in Ph+ Adult ALL
Official title: A Randomized Controlled Study of Dasatinib Combined With Reduced Intensive Consolidation Chemotherapy in Newly Diagosed Philadelphia Chromesome Positive Adult 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
Tyrosine Kinase Inhibitor
Consolidation Chemotherapy
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2021-08-30
Enrollment: 60
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 intensive chemotherapy has markedly improved the outcomes of philadelpha-positive lymphoblastic leukemia (Ph+ ALL). However, a considerable proportion of patients failed to complete the intended chemotherapy and some even died early. The optimal balance between the intensity of chemotherapy and safety should be explored. In this study, Ph+ ALL patients who achieve complete remission (CR) after VP regimen (vincristine and prednisone) plus dasatinib as induction are enrolled and then the participants will receive different consolidation chemotherapy. Patients in the group A will continue to use VP regimen plus dasatinib, while the group B receives hyper-CVAD/methotrexate-cytarabine regimen plus dasatinib. The measurable residual disease (MRD), CR, adverse effects (AE), overall survival (OS) and disease free survival (DFS) will be observed to determine the proper consolidation chemotherapy regimen.

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. The use of tyrosine kinase inhibitors (TKI) plus intensive chemotherapy has markedly improved the outcomes of Ph+ ALL. However, it's reported that 74% pf patients failed to complete the intended chemotherapy, and early death occured in a considerable proportion of patients during induction. The optimal balance between the intensity of chemotherapy and safety need to be explored. In this study, Ph+ ALL patients are enrolled. The participants will receive dasatinib and induction chemotherapy using VP regimen (vincristine and prednisone) to achieve complete remission (CR). Then the participants will be randomly divided into two groups. The subjects inthe group A will continue to use VP regimen plus dasatinib as consolidation, while the patients in the group B receive hyper-CVAD/methotrexate-cytarabine regimen plus dasatinib. The measurable residual disease (MRD), CR, adverse effects (AE), overall survival (OS) and disease free survival (DFS) will be observed to determine the proper consolidation chemotherapy regimen.

Eligibility criteria: Inclusion Criteria:

* 18-65 years old, newly diagnosed as Ph+ALL.
* Sign the informed consent.
* Accept consolidation chemotherapy.
* 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.
* Do not accept follow-up.

Primary outcomes:
measure: Percentage of Participants 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 Participants 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 consolidation chemotherapy until disease progression, the end of follow-up or the date of death from any cause, whichever came first.
measure: overall survival (OS), months
timeFrame: From date of consolidation chemotherapy until the end of follow-up or the date of death from any cause, whichever came first.
measure: adverse effects (AE)
timeFrame: From date of consolidation chemotherapy until the end of follow-up or the date of death from any cause, whichever came first.
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: