Decitabine, Venetoclax and Blinatumomab for Maintenance Following HSCT in Patients With Ph-Negative B-ALL

Official title

A Multicenter, Prospective, Phase II Study of Decitabine, Venetoclax and Blinatumomab for Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Patients With Ph-Negative B-Cell Acute Lymphoblastic Leukemia

Overview

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

• Drug Decitabine, 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)

Primary outcome measures

• PFS [Time frame: 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]

Secondary outcome measures (4)

• OS [Time frame: 2 years after allogenetic HSCT]
• CIR [Time frame: 2 years after allogenetic HSCT]
• TEAE [Time frame: From the start of each cycle to 30 days after the end]
• GRFS [Time frame: 2 years after allogenetic HSCT]

Eligibility criteria

Inclusion criteria

• 1.Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent an alloHSCT as follows:

• patients in CR1 with high-risk features,including adverse clinical features, cytogenetic or molecular alterations according to NCCN 2023.V3.
• patients lack of achievement of complete remission after standard induction chemotherapy.
• patients with detectable minimal residual disease pre-transplantation.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Soochow University — Suzhou

Publications

• Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067. PMID 41671463

Identifiers

NCT: NCT06393985 · FirstSoochowU-DVB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗