Conditioning Regimen Containing Melphalan and Cladribine for Refractory / Relapsed AML

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Bu/Cy regimen; Drug: MCBC regimen

• Study Type: Interventional
• Enrollment (Estimated): 237
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

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 :

  1. ) Uncontrolled or symptomatic angina history.
  2. ) Myocardial infarction less than 6 months away from the study.
  3. ) Have a history of arrhythmia requiring drug treatment or severe clinical symptoms.
  4. ) Uncontrolled or symptomatic congestive heart failure ( > NYHA class 2 ).
  5. ) The ejection fraction is lower than the lower limit of the normal range.
• Researchers evaluated that is not suitable for the group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: control arm; 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; control group, the standard conditioning regimen Busulfan/Cyclophosphamide; Other Names: classic group
Experimental: MCBC group; 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; 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; Other Names: experiment group

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): November 24, 2023
• Primary Completion (Estimated): October 20, 2028
• Study Completion (Estimated): October 20, 2028

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: IIT2023023-EC-2

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