Venetoclax Combining With Fludarabine and Melphalan as Conditioning Regimen for Allo-HSCT

Venetoclax Combining With Fludarabine and Melphalan as Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation for Older Patients With Hematologic Malignancies

venetoclax combining with fludarabine and melphalan as conditioning regimen prior to allogeneic hematopoietic stem cell transplantation for older patients with hematologic malignancies

Study Overview

• Status: Recruiting
• Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; Hematologic Malignancy; Older Patients
• Intervention / Treatment: Combination product: venetoclax combining with fludarabine and melphalan

Detailed Description

It was a phase Ⅱ clinical trial of new designed reduced-intensity conditioning regimen for older patients accepting allogeneic hematopoietic stem cell transplantation treatment. The regimen consisted of venetoclax combining with fludarabine and melphalan.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hangzhou, China
    • Recruiting
    • Sir Run Run Shaw Hospital, College of medicine, Zhejiang University
    • Contact: Haowen Xiao, MD; Phone Number: +86057187236706; Email: xiaohaowen@zju.edu.cn
  • Hangzhou, China
    • Recruiting
    • Zhejiang Provincial People's Hospital
    • Contact: Jianping Lan, MD; Phone Number: +8657187236706; Email: lanjp@163.com
  • Ningbo, China
    • Recruiting
    • Ningbo Hospital of Zhejiang University
    • Contact: Guifang Ouyang, MD; Phone Number: +86057187233801; Email: luoyijr@163.com
  • Ningbo, China
    • Recruiting
    • The Affiliated People's Hospital of Ningbo University
    • Contact: Ying Lu, MD; Phone Number: +86057187236706; Email: luying741107@qq.com
  • Wenzhou, China
    • Recruiting
    • The First Affiliated Hospital of Wenzhou Medical University
    • Contact: Yi Chen, MD; Phone Number: +8657187236706; Email: chenyi19527@163.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University
    • Hangzhou, Zhejiang, China
      • Recruiting
      • First Affiliated Hospital of Zhejiang Chinese Medicine University
      • Contact: Baodong Ye, MD; Phone Number: +8657187236706; Email: 13588453501@qq.com
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Second Affiliated Hospital of Zhejiang University, School of Medicine
      • Contact: Yang Xu, MD; Phone Number: +8657187236706; Email: zjuyujian@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age older than 50 years
2. Patients diagnosed with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome according to WHO diagnostic criteria.
3. Patients who achieved complete remission before transplantation.
4. Patients who have alternative donors and plane to accept allogeneic hematopoietic stem cell transplantation treatment.
5. ECOG body status score 0-2.
6. Good organ function level: ANC (neutrophil absolute value >=1.0x10^9/L; PLT >=30x10^9/L; HB >=80g/L; Tibil <=1.5 ULN; ALT / AST <=2.5 ULN; bun / Cr <=1.5 ULN; LVEF >=50%).
7. Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing.

Exclusion Criteria:

1. Patients who didn't achieved complete remission before transplantation (bone marrow smear: proportion of primordial cells >=5%) or any extramedullary recurrence.
2. Patients who were previously known to be resistant to venetoclax.
3. In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate the super pretreatment scheme.
4. Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of super pretreatment.
5. In patients with severe renal insufficiency, the renal function index (CR) is more than 2 times of the upper limit of the normal value (ULN), or the 24-hour creatinine clearance rate (CR) is less than 50ml / min, the researchers evaluated that they could not tolerate the super pretreatment scheme.
6. In patients with severe active infection, the researchers evaluated that they could not tolerate the pretreatment.
7. Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study.
8. Other reasons why the researchers could not be selected.

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: treatment group; older patients accepting venetoclax combining with fludarabine and melphalan as conditioning regimen prior to allogeneic hematopoietic stem cell transplantation treatment	Combination product: venetoclax combining with fludarabine and melphalan; Venetoclax 400mg/day，oral，day-8～day-2; Fludarabine, 30mg/m2/day，intravenous，d-7～d-3；Melphalan, 140mg/ m2/d，intravenous，day-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease free survival	2-year DFS	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of toxic reaction	2-year incidence of toxic reaction	2 year
overall survival	2-year OS	2 year
cumulative incidence of relapse	2-year incidence of relapse	2 year
incidence of acute and or chronic graft verus host disease	2-year incidence of cGVHD	2 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: Second Affiliated Hospital, School of Medicine, Zhejiang University; Sir Run Run Shaw Hospital; Zhejiang Provincial People's Hospital; First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Zhejiang Chinese Medical University; The Affiliated People's Hospital of Ningbo University; Ningbo Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Actual): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 20, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Venetoclax; Melphalan; Fludarabine
• Other Study ID Numbers: ZJU-HSCT-RIC

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