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

Precursor Cell Lymphoblastic Leukemia-Lymphoma Clinical Trial

Official title:

A Randomized Controlled Study of Dasatinib Combined With Reduced Intensive Consolidation Chemotherapy in Newly Diagosed Philadelphia Chromesome Positive Adult Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05026229
• Other study ID #: XJTU1AF-CRF-2020-002-2
• Status: Recruiting
• Phase: N/A
• Start date: September 6, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: August 2021
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: Pengcheng He
• Phone: 0086-18991232609
• Email: hepc[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• ALL, Adult
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• dasatinib plus consolidation chemotherapy with vincristine and prednisone
After induction therapy, the patients in the 'Dasatinib, Vincristine and Prednisone' group will receive dasatinib and consolidation chemotherapy with vincristine and prednisone.
• dasatinib plus consolidation chemotherapy with high-dose methotrexate and cytarabine
After induction therapy, the patients in the 'Dasatinib, Methotrexate and Cytarabine' group will receive dasatinib and consolidation chemotherapy with high-dose methotrexate and cytarabine.

Locations

Country	Name	City	State
China	First Affiliated Hospital of Xian Jiaotong University	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Measurable Residual Disease (MRD) Positivity	MRD refers to the subclinical levels of residual leukemia.	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.
Primary	Percentage of Participants with Complete Remission (CR)	CR means that the blood counts have returned to normal, the leukemia cannot be seen when a bone marrow sample is examined under the microscope, and the signs and symptoms of the ALL are gone.	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	disease-free survival (DFS), months	The measure of time after consolidation chemotherapy during which no sign of ALL is found.	From date of consolidation chemotherapy until disease progression, the end of follow-up or the date of death from any cause, whichever came first.
Secondary	overall survival (OS), months	The length of time from the date of diagnosis that Ph+ ALL patients are still alive.	From date of consolidation chemotherapy until the end of follow-up or the date of death from any cause, whichever came first.
Secondary	adverse effects (AE)	An adverse effect is any untoward medical occurrence in clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	From date of consolidation chemotherapy until the end of follow-up or the date of death from any cause, whichever came first.