Menin inhibitor maintenance after allogeneic stem cell transplant

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

This project will try menin inhibitor maintenance to see if it helps people with acute leukemia after allogeneic stem cell transplant who have KMT2A or related gene changes.

Quick facts

• Study type: Observational
• Enrollment: 20 (estimated)
• Ages: 15 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (other)
• Drugs / interventions: ruxolitinib
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07559695 on ClinicalTrials.gov

What this trial studies

This is an observational, real-world study of menin inhibitor maintenance given as part of routine care after allo-HSCT. Eligible patients receive a menin inhibitor chosen by their treating physician (examples include revumenib, ziftomenib, BN104, HMPL-506, or similar agents), with dosing, start time, and duration determined clinically. The study imposes no extra interventions and collects efficacy and safety data at each treatment cycle and during post-treatment survival follow-up. The protocol is conducted at The First Affiliated Hospital of Soochow University and follows patients from initiation of maintenance through survival follow-up.

Who should consider this trial

Good fit: Ideal candidates are people aged 15 or older with acute leukemia (AML, ALL, or MPAL) who are in CR/CRh/CRi after allo‑HSCT (at least 30 days post‑graft) and who are starting menin inhibitor maintenance, particularly those with KMT2A rearrangements, NPM1 (without FLT3 mutations), NUP98 rearrangements, or other menin‑dependent subtypes.

Not a fit: Patients without menin‑KMT2A‑dependent molecular features, those unable to tolerate menin inhibitors, or those with uncontrolled medical issues (for example severe active GVHD) are unlikely to benefit from this maintenance approach.

Why it matters

Potential benefit: If successful, this approach could lower relapse risk and improve long-term survival for patients with KMT2A‑related acute leukemia after allo‑HSCT.

How similar studies have performed: Early trials of menin inhibitors in relapsed or refractory leukemia with KMT2A fusions have shown promising remission rates, but use as post‑HSCT maintenance remains largely untested and observational.

Eligibility criteria

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.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (RECRUITING)

Study contacts

• Principal investigator: Su-ning Chen, M.D. — The First Affiliated Hospital of Soochow University
• Study coordinator: Su-ning Chen, M.D.

Conditions: Menin Inhibitors, Acute Leukemia, Post Hematopoietic Stem Cell Transplantation, Maintenance Therapy, KMT2A Rearrangement, NPM1 Mutation, NUP98 Gene Rearrangement