Azacitidine Combined with Donor Lymphocyte Infusion for Acute Myeloid Leukemia Post-transplant Relapse Prevention.

Phase 2

Not yet recruiting

• Conditions: Acute Myeloid Leukemia (AML); Relapse
• Interventions: Drug: Azacitidine (AZA)

• Registration Number: NCT06754540
• Lead Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary

This study is single-center, single-arm, prospective, Phase II clinical trial with the primary objective of assessing the effectiveness of azacitidine combined with donor lymphocyte infusion (DLI) in the prevention of recurrence after high-risk haploid hematopoietic stem cells of AML.

At the screening/baseline period, informed consent is obtained and the inclusion/exclusion criteria are checked. Plan to enroll 51 patients, and collect demographic data, medical history data, vital signs, physical examination and laboratory tests (blood routine; urine routine; liver and kidney function;Immune indicators: T cell subsets, Treg, etc.), pregnancy tests for female patients and other necessary auxiliary inspections.The time to start treatment is from the +90 to +180 days after high-risk AML haploid hematopoietic stem cell transplantation.

Detailed Description

1.Basic solution: Azacitidine is administered subcutaneously at 32 mg/m2/d for five consecutive days, starting no earlier than day +90 after HSCT, then repeated every 28 days for a total of twelve cycles. DLI is administered after an interval of 48 hours. Prophylactic DLI is given in escalating doses every four to six weeks for a total of three to four doses.The initial dose of DLI for haploid transplant patients is 1×10\^5 CD3+/kg receptor weight lymphocytes gradually increased to 5×10\^5, 1×10\^6 and (2\~5)×10\^6 CD3+ Lymphocytes.

1. Start time of medication: +90 \~ +120 days after transplantation.

2. Donor lymphocyte infusion was preceded by anti-anaphylaxis,such as promethazine and hormone therapy was prohibited.

3. In the course of AZA and DLI intervention, other targeted drugs such as venetoclax or chemotherapy drugs can be added on the basis of AZA if MRD or MRD increase (\>1log) ,DLI continues as planned.

2.Stop treatment: Occurrence of any of the following conditions:

1. Life-threatening complications.

2. Acute GVHD above II degree; chronic GVHD above moderate manifestations or overlapping syndrome; No chronic GVHD is observed if acute GVHD remission is observed after discontinuation for 1 to 2 months, then preventive treatment is started again .

3. Hematologic recurrence, graft rejection or bone marrow donor chimerism \<90%.

Study Timeline

• Study First Submitted: 2024-12-29
• Study First Submitted QC: 2024-12-30
• Status Verified: 2025-01
• Study First Posted: 2025-01-01
• Last Update Submitted: 2025-01-14
• Study Start: 2025-01-16
• Last Update Posted: 2025-01-17
• Primary Completion: 2027-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

Patients enrolled must meet the following criteria:

1. ≥18 years old and ≤70 years old, male or female;

2. Patients with haploid peripheral blood stem cell transplantation of AML;

3. All patients received BU based myeloablative conditionings;

4. A diagnosis of high-risk AML is one of the following:

   ① Patients without morphologic CR before transplantation, including patients with initial refractory disease and recurrence.

   ② AML with poor prognosis (Standardized diagnosis and prognostic stratification of acute myeloid leukemia based on ELN edition which was 2022 Year) .

5. Blood routine: neutrophils ≥1×10^9/L, platelet ≥50.0×10^9/L;

6. There is no active grade II or higher acute GVHD or moderate or severe chronic GVHD;

7. The ECOG score is 0 to 2;

8. Donor lymphocytes are available;

9. The patient must be able to understand and be willing to participate in the study and sign an informed consent form.

Exclusion Criteria

• Possible subjects who meet any of the following criteria will be excluded from the trial:

  1. Those who are allergic to known azacitidine or interferon
  2. Patients with active acute GVHD;
  3. Patients with moderate or more chronic GVHD;
  4. Non-haploid donor transplants;
  5. Patients who have not achieved complete remission after transplantation;
  6. AML recurrence after transplantation (bone marrow, peripheral blood primitive cells ≥5% or extramedullary recurrence), or graft rejection, bone marrow donor cell chimeric rate (STR) <90%;
  7. Patient blood routine: ANC<1.0×10^9/L or PLT<50×10^9/L;
  8. Combined with severe organ dysfunction:liver function (AST/ALT) >3 times normal upper limit; the direct bilirubin > 3 times normal upper limit; renal function (Cr) < 50mL/min or >1.5 times normal upper limit, regardless of hemodialysis treatment;
  9. Patient with severe active infection;
  10. Pregnant or lactating women;
  11. Have received other interventions or are receiving other research drugs before the study begins;
  12. At the discretion of the investigator, other dangerous complications may result.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AZA-DLI for acute myeloid leukemia post-transplant relapse preventiont	Azacitidine (AZA)	One arm,Azacitidine is administered subcutaneously at 32 mg/m2/d for five consecutive days, starting no earlier than day +90 after HSCT, then repeated every 28 days for a total of twelve cycles. DLI is administered after an interval of 48 hours. Prophylactic DLI is given in escalating doses every four to six weeks for a total of three to four doses.The initial dose of DLI for haploid transplant patients is 1×10\^5 CD3+/kg receptor weight lymphocytes gradually increased to 5×10\^5, 1×10\^6 and (2\~5)×10\^6 CD3+ Lymphocytes

Primary Outcome Measures

Name	Time	Method
Leukemia-free survival (LFS) time	From the date of transplantation, assessed up to 1 year after transplantation.	Summary statistics for LFS time will be computed for all patients.

Secondary Outcome Measures

Name	Time	Method
overall survival (OS)	From the date of transplantation, assessed up to 1 year after transplantation.	The method of Kaplan and Meier will be used to estimate the distribution of overall survival. Cox proportional hazards regression analysis will be used to model the association between overall survival and covariates of interest.
Cumulative incidence of relapse (CIR)	From the date of transplantation, assessed up to 1 year after transplantation.	Use the method of Gooley et al to estimate the cumulative incidence of relapse.
Cumulative incidence of acute and chronic GVHD	From the date of transplantation, assessed up to 1 year after transplantation.	Patients diagnosed with acute and chronic GVHD were recorded after DLI intervention.The definition of acute GVHD by national Institutes of Health (NIH) divides acute GVHD into classical acute GVHD and delayed acute GVHD
NRM	NRM	The proportion of transplant-related deaths was recorded.
Incidence of toxicity of the regimen	From the date of transplantation, assessed up to 1 year after transplantation.	Descriptive statistics will be used to summarize adverse events.