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

Phase 2

Recruiting

• Conditions: B-cell Acute Lymphoblastic Leukemia
• Interventions: Drug: Decitabine, venetoclax and blinatumomab

• Registration Number: NCT06393985
• Lead Sponsor: The First Affiliated Hospital of Soochow University

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.

Study Timeline

• Status Verified: 2024-04
• Study Start: 2024-04-25
• Study First Submitted: 2024-04-27
• Study First Submitted QC: 2024-04-27
• Study First Posted: 2024-05-01
• Last Update Submitted: 2024-11-17
• Last Update Posted: 2024-11-19
• Primary Completion: 2026-04-25
• Study Completion: 2027-04-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Decitabine,venetoclax and blinatumomab	Decitabine, venetoclax and blinatumomab	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (1)

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China