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

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

Detailed Description
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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.

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

Conditions
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Hematologic Malignancy, Older Patients, Allogeneic Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Combination Product: venetoclax combining with fludarabine and melphalan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age older than 50 years Patients diagnosed with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome according to WHO diagnostic criteria. Patients who achieved complete remission before transplantation. Patients who have alternative donors and plane to accept allogeneic hematopoietic stem cell transplantation treatment. ECOG body status score 0-2. 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%). Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing. Exclusion Criteria: Patients who didn't achieved complete remission before transplantation (bone marrow smear: proportion of primordial cells >=5%) or any extramedullary recurrence. Patients who were previously known to be resistant to venetoclax. 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. Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of super pretreatment. 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. In patients with severe active infection, the researchers evaluated that they could not tolerate the pretreatment. Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study. Other reasons why the researchers could not be selected.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>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<br>* Venetoclax 400mg/day，oral，day-8～day-2; Fludarabine, 30mg/m2/day，intravenous，d-7～d-3；Melphalan, 140mg/ m2/d，intravenous，day-2<br>|

What is the study measuring?
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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 |