Hypomethylating Agent and Venetoclax After Allo-HSCT in Patients With High-risk Myeloid Malignancies.

NCT05841771 | Recruiting Phase 2 DMC

• 1 other identifier: SHSYXY-AZA-VEN-202301
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of the study is to evaluate the efficacy and safety of maintenance therapy with hypomethylating agent and Venetoclax to improve leukemia free survival for high-risk myeloid malignancies after allogeneic hematopoietic stem cell transplantation .

Conditions

Hypomethylating Agent; Venetoclax; Myeloid Malignancy

Outcome Measures

Primary Outcomes (1)

• Leukemia-free survival (LFS) time

  Summary statistics for LFS time will be computed for all patients.

  From the date of transplantation, assessed up to 1 year after transplantation.

Secondary Outcomes (3)

• Cumulative incidence of relapse

  From the date of transplantation, assessed up to 1 year after transplantation.

• Overall survival

  From the date of transplantation, assessed up to 1 year after transplantation.

• Incidence of toxicity of the regimen

  From the date of transplantation, assessed up to 1 year after transplantation.

Study Arms (1)

AZA-VEN maintenance

EXPERIMENTAL

hypomethylating agents (azacytidine 32mg/m2 or decitabine 5mg/m2) for 5 days and venetoclax 400mg/d for 7 days, repeated every 28 days until up to 1-year posttransplant.

Drug: Venetoclax; Drug: Azacitidine or decitabine

Interventions

Venetoclax DRUG

Participants will receive maintenance therapy with venetoclax and azacitidine or decitabine after allogeneic stem cell transplantation. Azacitidine will be administered once daily subcutaneously (32mg/m2/d) on days 1-5, and venetoclax will be administered once daily orally (400mg/day) on days 1-7. If the patient is refractory or allergic to azacitidine, they will receive decitabine. Decitabine will be administered intravenously (5mg/m2/d) on days 1-5. If the patient is treated with CYP450 inhibitors(such as posaconazole or voriconazole), the dose of venetoclax will reduce to 100 mg once daily on days 1-7. Maintenance therapy will start from the 60th to 120th days after allogeneic hematopoietic stem cell transplantation and repeat every 28 days for up to 10 cycles within the first year after transplantation.

Also known as: BCL-2 inhibitor

AZA-VEN maintenance

Azacitidine or decitabine DRUG

azacytidine 32mg/m2 or decitabine 5mg/m2

Also known as: Hypomethylating Agent

AZA-VEN maintenance

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with AML or MDS and have received allogeneic hematopoietic cell transplantation;
• Patients with AML must have one of the following high-risk factors: Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML； require more than 2 courses of induction chemotherapy to reach complete remission； Extramedullary myeloid malignancy；≥CR2； Presence of measurable residual disease at the time of HSCT. \*
• Patients with MDS must have one of the following high-risk factors: IPSS-R scores are high-risk or very high-risk； Presence of TP53 mutation； Presence of measurable residual disease at the time of HSCT. \*
• CBC: ANC ≥ 1.0 × 10e9/L, Hb ≥ 80g/L, and PLT ≥ 50 × 10e9/L；
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Presence of measurable residual disease at the time of HSCT is defined as the following: Blast percentage in bone marrow detected by flow cytometry ≥0.01%； Presence of fusion gene or mutated gene by qPCR.

You may not qualify if:

• Concurrent use of targeted drugs ;
• Resistant to Venetoclax before transplantation;
• Allergic to decitabine , Azacitidine or venetoclax;
• Active grade II or higher acute GVHD ;
• Active moderate or severe chronic GVHD ;
• Diseases recurrence (abnormal myeloid cells detected by flow cytometry \>0.01%, presence of WT1 or other genes, or extramedullary malignancy ), percentage of donor cells in bone marrow \<90% or graft rejection:
• CBC: ANC \< 1.0 × 10e9/L, or PLT \< 50 × 10e9/L；
• Severe organ dysfunction: Elevated Aspartate transaminase (AST) /alanine transaminase (ALT), or direct bilirubin \>3 times upper limit of normal; Creatinine clearance (Ccr)\<50mL/min or serum creatinine \>1.5 times upper limit of normal, whether hemodialysis treatment is performed;
• Active uncontrolled systemic fungal, bacterial, or viral infection
• Pregnant or lactating women;
• Other severe complications and not suitable judged by researchers.

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Shanghai Jiao Tong University School of Medicine Affilated Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

RECRUITING

MeSH Terms

Interventions

venetoclax; PTH2 protein, human; Azacitidine; Decitabine

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Liping Wan, M.D.

  Shanghai Jiao Tong University School of Medicine Affiliated Shanghai General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xueying Ding, Ph.D.

CONTACT

8621-36126060; shiyicss@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director of Department of Hematology

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: May 3, 2023
• Study Start: January 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: August 9, 2024

Record last verified: 2024-08

Locations

CN (1)