In the treatment of Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) among adult patients, therapeutic outcomes remain suboptimal despite advances in chemotherapy and immunotherapy. A subset of adults with Ph- B-ALL have comorbidities or physiological limitations that preclude the safe administration of intensive regimens. In recent years, tumor immunotherapy has demonstrated promising safety and efficacy profiles in refractory or relapsed Ph- B-ALL across a wide spectrum of adult ages. These findings suggest that broader application of immunotherapy may represent a critical strategy to improve survival in this population. In this study, we propose a regimen that combines immuno-targeted agents with low-intensity chemotherapy for newly diagnosed adult patients with Ph- B-ALL. Our primary objective is to increase the rate of measurable residual disease (MRD)-negative complete remission (CR) following induction therapy, reduce the risk of relapse, and ultimately enhance overall survival.
In this open-label, single-arm, Phase II study, prospective clinical trial, a total of 53 Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) patients will be enrolled. The primary endpoint is measurable residual disease (MRD)-negative complete remission (CR) rate after induction therapy. The first cycle of induction therapy is administered with Inotuzumab ozogamicin (INO), Venetoclax (VEN), and a combination of low-dose chemotherapy. The second cycle of induction therapy is Blinatumomab (Blino) plus VEN regimen. Alternatively, the first cycle of induction therapy is a combination of VEN and low-dose chemotherapy, and the second cycle of induction therapy is methotrexate (MTX) plus cytarabine (Ara-C) plus VEN regimen. Subsequent consolidation and maintenance therapy consist of low-dose chemotherapy, Blino, and VEN. Patients can receive chimeric antigen receptor T-Cell (CAR-T) Immunotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) or receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. Study patients are scheduled for follow-up for at least 5 years after the end of maintenance therapy. The purpose of current study is to determine the efficacy and safety of low-dose chemotherapy combined with immuno-targeted drugs in newly diagnosed adult patients with Ph- B-ALL.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Anti-tumor alkaloids
Alkylating agent
Glucocorticoids
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)
A humanized monoclonal antibody-drug conjugate targeting CD22
Bi-specific anti-CD19/CD3 antibodies
Cell cycle-specific antitumor drug
Antifolate antineoplastic drug
Pyrimidine antimetabolites
Glucocorticoids
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGMRD-negative complete remission rate measured by flow cytometry.
No immature cells were detected by flow cytometry when CR criteria were met after induction therapy.
Time frame: After induction (4 week)
Complete remission (CR) rate
Time frame: an expected average of 3 months
Overall survival (OS)
From the date of registration to the date of death resulting from any cause.
Time frame: Up to 5 years post-registration
Relapse free survival (RFS)
From the date of complete remission (CR) until the date of documented relapse or death due to any cause or last follow-up.
Time frame: Up to 5 years post-registration
Disease-free Survival (DFS)
From CR1 to relapse, death from any cause or last follow-up.
Time frame: Up to 5 years post-registration
Mortality
Time frame: Day 30 and Day 60 of induction therapy initiation
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