A Study of Dasatinib Plus Reduced Intensive Consolidation Chemotherapy in Ph+ Adult ALL

Xi'an Jiaotong University

Status: Unknown

Conditions: ALL, Adult; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Philadelphia-Positive Acute Lymphoblastic Leukemia

Treatments: Drug: dasatinib plus consolidation chemotherapy with high-dose methotrexate and cytarabine; Drug: dasatinib plus consolidation chemotherapy with vincristine and prednisone

Study type: Interventional

Funder types: Other

Identifiers

NCT05026229

XJTU1AF-CRF-2020-002-2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Dasatinib, Vincristine and Prednisone

Experimental group

Description:

After induction therapy, the patients in the 'Dasatinib, Vincristine and Prednisone' group will receive dasatinib and consolidation chemotherapy with vincristine and prednisone.

Treatment:

Drug: dasatinib plus consolidation chemotherapy with vincristine and prednisone

Dasatinib, Methotrexate and Cytarabine

Experimental group

Description:

After induction therapy, the patients in the 'Dasatinib, Methotrexate and Cytarabine' group will receive dasatinib and consolidation chemotherapy with high-dose methotrexate and cytarabine.

Treatment:

Drug: dasatinib plus consolidation chemotherapy with high-dose methotrexate and cytarabine