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

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

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.

Study Overview

• Status: Recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Decitabine, venetoclax and blinatumomab

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaowen Tang, Ph.D; Phone Number: 67781525; Email: xwtang1020@163.com
• Study Contact Backup: Name: Depei Wu, Ph.D; Phone Number: 67781856; Email: drwudepei@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • the First Affiliated Hospital of Soochow University
      • Contact: Xiaowen Tang, Ph.D; Phone Number: 67781525; Email: xwtang1020@163.com
      • Principal Investigator: Xiaowen Tang, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Decitabine,venetoclax and blinatumomab	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	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.)	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

Outcome Measure	Measure Description	Time Frame
OS	Overall survival (OS) is defined as the period from the date of allogenetic HSCT to the date of death.	2 years after allogenetic HSCT
CIR	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.	2 years after allogenetic HSCT
TEAE	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.	From the start of each cycle to 30 days after the end
GRFS	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.	2 years after allogenetic HSCT

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Study Chair: Xiaowen Tang, Ph.D, the First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2024
• Primary Completion (Estimated): April 25, 2026
• Study Completion (Estimated): April 25, 2027

Study Registration Dates

• First Submitted: April 27, 2024
• First Submitted That Met QC Criteria: April 27, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: HSCT; maintenance therapy; Ph-negative B-ALL
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Decitabine; Venetoclax; Blinatumomab
• Other Study ID Numbers: FirstSoochowU-DVB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No