A Real-world Study on the Efficacy and Safety of Menin Inhibitors as Maintenance After Allo-HSCT

A Real-world Study on the Efficacy and Safety of Menin Inhibitors as Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation

The objective of this observational study is to evaluate the efficacy and safety of menin inhibitor maintenance therapy in patients with acute leukemia who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Eligible patients will receive menin inhibitor maintenance therapy as part of their routine clinical practice. Acceptable agents include, but are not limited to, Revumenib, BN104, Ziftomenib, HMPL-506, or other menin-KMT2A interaction inhibitors. This study imposes no additional interventions on clinical management. The specific menin inhibitor, initiation timing, dose adjustments, and treatment duration are determined at the investigator's discretion based on the patient's individual condition and clinical circumstances.

Patients will enter the follow-up phase upon initiation of menin inhibitor maintenance therapy. Efficacy and safety will be assessed at every cycle during the treatment period. Following the completion of treatment, survival follow-up visits will be conducted every three cycles. The primary endpoint is 2-year relapse-free survival rate since enrollment. The secondary endpoints included overall survival, event-free survival, cumulative incidence of relapse, non relpase related mortality and safety.

Study Overview

• Status: Recruiting
• Conditions: Acute Leukemia; Maintenance Therapy; NPM1 Mutation; Post Hematopoietic Stem Cell Transplantation; KMT2A Rearrangement; Menin Inhibitors; NUP98 Gene Rearrangement

Detailed Description

AML with KMT2A rearrangements are grouped as a high risk subtype. Allogenic hematopoietic stem cell transplantation is the only curative strategy for this subtype. However, patients with KMT2A rearrangements have a high incidence of relapse rates. Menin inhibitors have shown promising remission rates in patients with relpased or refractory patients haboring specific fusions including KMT2A rearrangements. The role of menin inhibitors in post-HSCT maintenance therapy remains unknown.

The objective of this observational study is to evaluate the efficacy and safety of menin inhibitor maintenance therapy in patients with acute leukemia who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Eligible patients will receive menin inhibitor maintenance therapy as part of their routine clinical practice. Acceptable agents include, but are not limited to, Revumenib, BN104, Ziftomenib, HMPL-506, or other menin-KMT2A interaction inhibitors. This study imposes no additional interventions on clinical management. The specific menin inhibitor, initiation timing, dose adjustments, and treatment duration are determined at the investigator's discretion based on the patient's individual condition and clinical circumstances.

Patients will enter the follow-up phase upon initiation of menin inhibitor maintenance therapy. Efficacy and safety will be assessed at every cycle during the treatment period. Following the completion of treatment, survival follow-up visits will be conducted every three cycles. The primary endpoint is 2-year relapse-free survival rate since enrollment. The secondary endpoints included overall survival, event-free survival, cumulative incidence of relapse, non relpase related mortality and safety.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Su-ning Chen, M.D.; Phone Number: (0086)13814881746; Email: chensuning@sina.com
• Study Contact Backup: Name: Hai-ping Dai, M.D.; Phone Number: (0086)13914086271; Email: daihaiping8@126.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Su-ning Chen, M.D.; Phone Number: +8613814881746; Email: chensuning@sina.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation and received post-transplant menin inhibitor maintenance therapy.

Description

Inclusion Criteria:

1. Age ≥ 15 years.
2. Patients diagnosed with acute leukemia (including AML, ALL, and MPAL) according to the World Health Organization (WHO 2022) criteria.
3. Must meet one of the following characteristics: a. Harboring an NPM1 gene mutation (without concurrent FLT3-ITD or FLT3-TKD mutation); b. Harboring a KMT2A gene rearrangement or KMT2A-PTD; c. Harboring a NUP98 gene rearrangement; d. Other acute leukemia subtypes dependent on the menin-KMT2A interaction, if evidenced, may be enrolled upon discussion with and approval from the principal research team.
4. Has undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), with ≥ 30 days elapsed since the date of graft infusion.
5. Received menin inhibitor maintenance therapy after allo-HSCT and meets the following conditions: a. Received at least ≥ 2 complete cycles (7 days per cycle) of menin inhibitor therapy, or cumulative medication duration ≥ 14 days; b. Patient was in a state of CR/CRh/CRi at the initiation of maintenance therapy.
6. No evidence of leukemia relapse during menin inhibitor maintenance therapy, defined as: a. Bone marrow blasts < 5%, and blasts do not exhibit morphological features of acute leukemia (e.g.Auer rods); b. No evidence of extramedullary leukemia (e.g. CNS leukemia or myeloid sarcoma).
7. The menin inhibitors used include but are not limited to: Revumenib, BN104, Ziftomenib, HMPL-506, or other menin-KMT2A interaction inhibitors.
8. Capable of understanding and voluntarily signing the informed consent form.
9. Complete clinical data.

Exclusion Criteria:

1. Presence of any of the following at the initiation of menin inhibitor maintenance therapy (including within 28 days prior to starting treatment): a. Morphologic relapse in bone marrow (bone marrow blasts ≥ 5%); b. Presence of leukemic cells in peripheral blood.
2. Active infection that is deemed uncontrolled by the investigator.
3. Severe organ dysfunction, including: a. Hepatic impairment: ALT or AST ≥ 5 × ULN (Upper Limit of Normal), or total bilirubin ≥ 3 × ULN; b. Severe renal impairment: eGFR < 30 ml/min/1.73 m²; c. Cardiac dysfunction: NYHA (New York Heart Association) Class III-IV.
4. Concurrent acute graft-versus-host disease (aGVHD) ≥ Grade 2 or chronic graft-versus-host disease (cGVHD) ≥ Grade 3, requiring corticosteroids ≥ 1 mg/kg and ≥ 3 types of immunosuppressive therapy (including CNI, ruxolitinib, belumosudil, etc.).
5. History of other malignancies requiring ongoing treatment (except for malignancies that have undergone curative treatment or are assessed to be in complete remission and require no systemic maintenance therapy or radiotherapy).
6. Any gastrointestinal disorder that may affect the intake or absorption of oral medications (e.g.dysphagia, gastroparesis, uncontrolled chronic diarrhea, intestinal GVHD, etc).
7. Patients deemed unsuitable for inclusion in this study by the investigator.
8. Severely missing clinical data, precluding efficacy or safety assessment.
9. Receipt of other maintenance therapies, including but not limited to hypomethylating agents, donor lymphocyte infusion (DLI), or other specific small-molecule targeted drugs.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Post-alloHSCT menin maintenance; Patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and received menin inhibitor maintenance therapy after transplantation. Menin inhibitors include but are not limited to Revumenib, BN104, Ziftomenib, HMPL-506, or other menin-KMT2A interaction inhibitors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year rate of RFS	It is measured as the proportions of numbers of patients with hematologic relapse to the numbers of the overall enrolled patients at 2 years from the first day of taking menin inhibitor post allo-HSCT.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival (OS): It is measured from the date of the first day of taking menin inhibitor post allo-HSCT to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.	2 years
EFS	Event-free survival(EFS): It is measured from he date from the first day of taking menin inhibitor post allo-HSCT to the first documented hematologic relapse, initiation of other maintenance therapy stragies such as hypomethylation agents, interferon, donor lymphocyte infusion, Bcl-2 inhibitor or death from any cause. Patients who die without evidence of relapse are typically censored at the last disease-free assessment.	2 years
CIR	Cumulative incidence of relapse (CIR): It is measured as the estimated rate of hematologic relapse or extramedullary relapse since the first day of taking menin inhibitor post allo-HSCT.	2 years
NRM	non-relapse mortality (NRM): It is measured the probability of death attributable to treatment-related complications or comorbidities, excluding disease relapse/progression since the first day of taking menin inhibitor post allo-HSCT.	2 years
Incidence and severity of GVHD	Incidence and severity of acute and chronic GVHD since the first day or taking menin inhibitor post allo-HSCT.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-/post-transplant MRD dynamics	Serial monitoring results of measurable residual disease status detected by qPCR or Ig/TR rearrangements since the first day of taking menin inhibitor.	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Su-ning Chen, M.D., The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: April 24, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: menin inhibitors maintenance

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No