A Study of TKI Maintenance Therapy Following Allo-HSCT in Newly Diagnosed 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

Study type: Interventional

Funder types: Other

Identifiers

NCT05024357

XJTU1AF-CRF-2020-002-1

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 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.

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. 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.

Enrollment: 80 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.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Dasatinib for 1 year

Experimental group

Description:

After the allo-HSCT treatment, the patients in this group will continue to take dasatinib orally for 1 year.

Treatment:

Drug: Dasatinib

Dasatinib for 6 months

Experimental group

Description:

After the allo-HSCT treatment, the patients in this group will receive dasatinib for 6 months.

Treatment:

Drug: Dasatinib