B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
Ph-negative B-ALL, HSCT, maintenance therapy
Brief summary
This study aims to evaluate whether maintenance therapy with decitabine, venetoclax and blinatumomab could improve the 2-year progression free survival (PFS) of patients with philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who had recently received an allogeneic stem cell transplant and in measurable residual disease-negative remission.
Detailed description
This is a phase Ⅱ, open-label, single-arm, multi-center study in patients with philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who had recently received an allogeneic stem cell transplant and in minimal residual disease-negative remission. In this study, patients will be treated with 4 cycles of maintence therapies for up to one year (or until intolerable toxicity, death, withdrawal, or study termination). In cycle one and three, patients will receive decitabine monotherapy, and in cycle two and four, patients will receive a combination of venetoclax and blinatumomab. This study aims to evaluate whether maintenance therapy with decitabine, venetoclax and blinatumomab could improve the 2-year progression free survival (PFS) of those patients, and explore the efficiency and safety.
Interventions
DRUGDecitabine, venetoclax and blinatumomab
Cycle1 and cycle3： Decitabine monotherapy,20 mg/m2 qd, d1-5,intravenous infusion; Cycle2 and cycle4: Venetoclax 200mg qd, d1-14, orally; Blinatumomab d4-17(Weight ≥45 kg, 9ug d4-6, 28ug d7-17; Weight \<45 kg, 5ug/m2 d4-6, 15ug/m2 d7-17;continuous intravenous infusion)
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 1.Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent an alloHSCT as follows: 1. patients in CR1 with high-risk features,including adverse clinical features, cytogenetic or molecular alterations according to NCCN 2023.V3. 2. patients lack of achievement of complete remission after standard induction chemotherapy. 3. patients with detectable minimal residual disease pre-transplantation. 4. patients in second and higher CR pre-transplantation. 2.Negative minimal residual disease prior to enrollment (FCM-MRD \<0.01% and fusion gene negative). 3.≥3 months post-transplantation. 4.hematopoietic reconstitution, i.e., ANC ≥0.5 x 109/L, and platelets \>20 x 109/L. 5.Eastern Cooperative Oncology Group (ECOG) score: 0-2. 6.Total serum bilirubin ≤ 3 x upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 5 x ULN, aspartate aminotransferase (AST) ≤ 5 x ULN. 7.Creatinine clearance ≥ 30 mL/min. 8.Provide informed consent.
Exclusion criteria
* 1.Patients with another malignant disease. 2.Patients with uncontrolled active infection. 3.Patients with left ventricular ejection fraction \< 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification. 4.Detectable minimal residual disease post-transplantation 5.Active GVHD requiring systemic steroid therapy. 6.Patients with uncontrolled active bleeding. 7.Pregnant and lactating women; patients of childbearing potential should be willing to practice methods of contraception throughout the study period. 8.Patients with other commodities that the investigators considered not suitable for the enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | From date of allogenetic HSCT until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years after allogenetic HSCT | Progression-free survival (PFS) was defined as the period from the date of allogenetic HSCT to the observed progression of the disease or the occurrence of death for any reason.(Progression is defined as more than 5% blast in the peripheral blood or bone marrow biopsy.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | 2 years after allogenetic HSCT | Overall survival (OS) is defined as the period from the date of allogenetic HSCT to the date of death. |
| CIR | 2 years after allogenetic HSCT | Cumulative incidence of relapse（CIR）is measured from the date of achievement of remission until the date of hematologic relapse, or MRD relapse. Patients who died without relapsing are counted as a competing cause of failure. |
| TEAE | From the start of each cycle to 30 days after the end | Treatment-emergent adverse event (TEAE; frequency, CTCAE grade） is defined as an AE observed after starting administration of the study treatment until 30 days from the end. |
| GRFS | 2 years after allogenetic HSCT | GVHD-free relapse-free survival (GRFS) is defined as the time from the date of allogenetic HSCT until the date of treatment-emergent acute GVHD III-IV, or treatment-emergent chronic GVHD that requires new or additional immunosuppressive treatment, or morphological relapse or death from any cause, whichever occurs first. |
Countries
China
Contacts
Primary ContactXiaowen Tang, Ph.D
Backup ContactDepei Wu, Ph.D
Outcome results
None listed