- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT07559695
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.
Aperçu de l'étude
Statut
Description détaillée
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.
Type d'étude
Inscription (Estimé)
Contacts et emplacements
Coordonnées de l'étude
- Nom: Su-ning Chen, M.D.
- Numéro de téléphone: (0086)13814881746
- E-mail: chensuning@sina.com
Sauvegarde des contacts de l'étude
- Nom: Hai-ping Dai, M.D.
- Numéro de téléphone: (0086)13914086271
- E-mail: daihaiping8@126.com
Lieux d'étude
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Jiangsu
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Suzhou, Jiangsu, Chine, 215006
- Recrutement
- The First Affiliated Hospital of Soochow University
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Contact:
- Su-ning Chen, M.D.
- Numéro de téléphone: +8613814881746
- E-mail: chensuning@sina.com
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Enfant
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria:
- Age ≥ 15 years.
- Patients diagnosed with acute leukemia (including AML, ALL, and MPAL) according to the World Health Organization (WHO 2022) criteria.
- 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.
- Has undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), with ≥ 30 days elapsed since the date of graft infusion.
- 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.
- 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).
- The menin inhibitors used include but are not limited to: Revumenib, BN104, Ziftomenib, HMPL-506, or other menin-KMT2A interaction inhibitors.
- Capable of understanding and voluntarily signing the informed consent form.
- Complete clinical data.
Exclusion Criteria:
- 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.
- Active infection that is deemed uncontrolled by the investigator.
- 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.
- 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.).
- 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).
- Any gastrointestinal disorder that may affect the intake or absorption of oral medications (e.g.dysphagia, gastroparesis, uncontrolled chronic diarrhea, intestinal GVHD, etc).
- Patients deemed unsuitable for inclusion in this study by the investigator.
- Severely missing clinical data, precluding efficacy or safety assessment.
- Receipt of other maintenance therapies, including but not limited to hypomethylating agents, donor lymphocyte infusion (DLI), or other specific small-molecule targeted drugs.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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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.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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2-year rate of RFS
Délai: 2 years
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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.
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2 years
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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OS
Délai: 2 years
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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.
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2 years
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EFS
Délai: 2 years
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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.
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2 years
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CIR
Délai: 2 years
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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.
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2 years
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NRM
Délai: 2 years
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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.
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2 years
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Incidence and severity of GVHD
Délai: 2 years
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Incidence and severity of acute and chronic GVHD since the first day or taking menin inhibitor post allo-HSCT.
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2 years
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Pre-/post-transplant MRD dynamics
Délai: 2 years
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Serial monitoring results of measurable residual disease status detected by qPCR or Ig/TR rearrangements since the first day of taking menin inhibitor.
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2 years
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Collaborateurs et enquêteurs
Les enquêteurs
- Chercheur principal: Su-ning Chen, M.D., The First Affiliated Hospital of Soochow University
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Autres numéros d'identification d'étude
- menin inhibitors maintenance
Informations sur les médicaments et les dispositifs, documents d'étude
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