Conditioning Regimen Containing Melphalan and Cladribine for Refractory / Relapsed AML

Study Overview
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Brief Summary
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This project is a prospective, multicenter, randomized controlled clinical study. The subjects were refractory / relapsed AML patients aged ≤ 60 years diagnosed by bone marrow cell morphology, immunology, genetics and therapeutic efficacy evaluation. The classical Bu / Cy scheme or MCBC scheme was used for pretreatment. The primary endpoint of the study was the 3-year recurrence-free survival rate after allogeneic hematopoietic stem cell transplantation, and the secondary endpoints were 3-year overall survival rate, recurrence rate, treatment-related mortality, and pretreatment-related toxicity.

Official Title
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Conditioning Regimen Containing Melphalan and Cladribine for Refractory / Relapsed AML

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: MCBC regimen
* Drug: Bu/Cy regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory / relapsed AML. Patients with a HLA matched related or unrelated donor (9 10/10) or haplo-identical related donor, plan to receive HSCT. Age ≤ 60 years old, men and women are not limited. The Eastern Oncology Collaborative Group Physical Status Assessment ( ECOG-PS ) was 0-2 points. Informed consent must be signed before the start of the study procedure. Informed consent must be signed by the patient or his or her immediate family members who are 18 years of age or older ; informed consent was signed by the legal guardian for children and adolescent patients under 18 years old. Considering the patient 's condition, if the patient 's signature is not conducive to the treatment of the disease, the informed consent is signed by the legal guardian or the patient 's immediate family. Exclusion Criteria: Have a history of cancer and have received any treatment for this tumor in the past 3 years. But remove superficial bladder cancer, skin basal cells or squamous cell carcinoma, cervical epithelium. Intraepithelial neoplasia ( CIN ) or prostatic intraepithelial neoplasia ( PIN ). MPAL. It is known that the serological reaction of HIV or active hepatitis C virus is positive. The inability to cooperate with the requirements of research, treatment and monitoring due to mental illness or other conditions. Pregnant patients or patients who could not take appropriate contraceptive measures during treatment. Previously received hematopoietic stem cell transplantation. Active heart disease, defined as one or more of the following : ) Uncontrolled or symptomatic angina history. ) Myocardial infarction less than 6 months away from the study. ) Have a history of arrhythmia requiring drug treatment or severe clinical symptoms. ) Uncontrolled or symptomatic congestive heart failure ( > NYHA class 2 ). ) The ejection fraction is lower than the lower limit of the normal range. Researchers evaluated that is not suitable for the group.

Ages Eligible for Study
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Maximum Age: 60 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: control arm<br>Busulfan/Cyclophosphamide, standard conditioning regimen as a control group. including Bu3.2mg/kg -5 -3d; Cy 80mg/kg，-2 -1d。 or alternative Bu/Cy regimen, Bu3.2mg/kg -9 -7d；Flu 30mg/m2 -6 -4d；Ara-C 2g/m2 -6 -4d；Cy 80mg/kg -3 -2d。 | Drug: Bu/Cy regimen<br>* control group, the standard conditioning regimen Busulfan/Cyclophosphamide<br>* Other names: classic group;|
| Experimental: MCBC group<br>using MCBC as conditioning regimen, Mel 60mg/ m2 -9 -8d, Cladribine 5 mg/m2 -9 -5d, Bu3.2mg/kg -5 -3d； Cy 30mg/kg -2 -1 d | Drug: MCBC regimen<br>* using MCBC as conditioning regimen, Mel 60mg/ m2 -9 -8d, Cladribine 5 mg/m2 -9 -5d, Bu3.2mg/kg -5 -3d； Cy 30mg/kg -2 -1 d<br>* Other names: experiment group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Free Survival | The AML relapse free survival post-HSCT | 3 year post-HSCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The overall survival post-HSCT | 3 year post-HSCT | 
| cumulative incidence relapse rate | cumulative incidence relapse rate post-HSCT | 3 year post-HSCT | 
| Non-relapse mortality | Non-relapse mortality post-HSCT | 3 year post-HSCT | 
| toxicity of conditioning regimen | Adverse events as assessed by CTCAE to evaluate conditioning related toxicity | 24w post-HSCT | 
| Immune reconstitution post-HSCT | Using lymphocyte subset panel to assess immune recovery post-HSCT | 24w post-HSCT |