Low-dose Cyclophosphamide or CNI in the Prevention of Acute Graft-versus-host Disease After gDLI

Official title

A Prospective Multicenter Randomized Controlled Clinical Trial Protocol for the Efficacy and Safety of Low-dose Cyclophosphamide or CNI in the Prevention of Acute Graft-versus-host Disease After gDLI

Overview

Assess the cumulative incidence of severe (III-IV) aGVHD after low-dose cyclophosphamide or CNI is used to after gDLI. Evaluate the overall survival rate (OS), non recurrent mortality rate (NRM), and recurrence rate (CIR) of two groups of patients; The complete response rate (CR) and partial response rate (PR) of patients with morphological/extramedullary recurrence, as well as the complete response rate and MRD response rate of patients with molecular recurrence. The incidence of adverse events such as infection, hemorrhagic cystitis, and cardiac events in two groups.

Detailed description

Assess the cumulative incidence of severe (III-IV) aGVHD after low-dose cyclophosphamide or CNI is used to after gDLI. Evaluate the overall survival rate (OS), non recurrent mortality rate (NRM), and recurrence rate (CIR) of two groups of patients; The complete response rate (CR) and partial response rate (PR) of patients with morphological/extramedullary recurrence, as well as the complete response rate and MRD response rate of patients with molecular recurrence. The incidence of adverse events such as infection, hemorrhagic cystitis, and cardiac events in two groups.

Efficacy Evaluation: Follow up observation of the difference in efficacy and safety between two groups in preventing severe (III-IV) aGVHD.

Primary Exploratory Endpoint: Assess the cumulative incidence of severe (III-IV) aGVHD after low-dose cyclophosphamide or CNI is used after gDLI.

Secondary Exploratory Endpoints:

1. 1-year overall survival rate (OS); 2. 1-year recurrence rate (CIR); 3. 1-year non recurrent mortality rate (NRM); 4. The complete response rate (CR) and partial response rate (PR) of patients with morphological/extramedullary recurrence, as well as the complete response rate and MRD response rate of patients with molecular recurrent minimal residual disease (MRD); 5. The incidence of adverse events such as infection, hemorrhagic cystitis, and cardiac events in two groups.

Interventions

• Drug PDCy
  Low dose Cy 30 mg/kg/d was administered on the 3rd and 4th day after gDLI to prevent GVHD
• Drug Non Cy
  Oral administration of low-dose CNI (CSA 25mg Q12H or FK506 0.25mg Q12H combined with azole fungal drugs) for 2 weeks to prevent GVHD at 0 days after gDLI

Primary outcome measures

• Assess the cumulative incidence of severe (III-IV) aGVHD after low-dose cyclophosphamide or CNI is used after gDLI. [Time frame: Until the end of the study]

Secondary outcome measures (5)

• 1-year overall survival rate (OS) [Time frame: 1 year after the last patient was enrolled]
• 1-year recurrence rate (CIR) [Time frame: 1 year after the last patient was enrolled]
• 1-year non recurrent mortality rate (NRM) [Time frame: 1 year after the last patient was enrolled]
• The complete response rate (CR) and partial response rate (PR) of patients with morphological/extramedullary recurrence, as well as the complete response rate and MRD response rate of patients with molecular recurrent minimal residual disease (MRD) [Time frame: 1 year after the last patient was enrolled]
• The incidence of adverse events such as infection, hemorrhagic cystitis, and cardiac events in two groups. [Time frame: 1 year after the last patient was enrolled]

Eligibility criteria

Inclusion criteria

• Subjects eligible for inclusion in this study must meet all of the following criteria:

• Patients with malignant hematological diseases undergo haploid/sibling incomplete matching/unrelated donor transplantation;
• Recurrence after transplantation (morphological, extramedullary, or molecular recurrence);
• Plan to administer granulocyte colony-stimulating factor mobilization donor lymphocyte infusion (gDLI) for treatment;
• No age, gender, or race restrictions;
• The physical condition assessment (ECOG-PS) of the Eastern Oncology Collaborative Group is 0-2 points;
• The patient or their authorized representative agrees to participate in the clinical trial and signs an informed consent form.

Exclusion criteria

• Subjects meeting any of the following criteria are not eligible for inclusion in this study:

• Siblings of matched donor transplant;
• Patients with other malignant tumors that require treatment;
• There are active infections, such as hepatitis B, hepatitis C, tuberculosis, etc;
• HIV serological reaction was positive;
• Suffering from mental illness or other conditions that cannot comply with research, treatment, and monitoring requirements;
• Pregnant patients or patients who are unable to take appropriate contraceptive measures during treatment;
• Active heart disease is defined as one or more of the following:

• Have a history of uncontrolled or symptomatic angina pectoris;
• Myocardial infarction less than 6 months prior to enrollment in the study;
• A history of arrhythmia requiring medication treatment or severe clinical symptoms;
• Uncontrolled or symptomatic congestive heart failure (\>NYHA level 2);
• The ejection fraction is below the lower limit of the normal range.
• Individuals who are allergic to any medication or component such as Cy, CNI, etc;
• The researchers believe that it is not suitable for participants.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06490562 · IIT2024034

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗