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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前:Su-ning Chen, M.D.
- 電話番号:(0086)13814881746
- メール:chensuning@sina.com
研究連絡先のバックアップ
- 名前:Hai-ping Dai, M.D.
- 電話番号:(0086)13914086271
- メール:daihaiping8@126.com
研究場所
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Jiangsu
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Suzhou、Jiangsu、中国、215006
- 募集
- The First Affiliated Hospital of Soochow University
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コンタクト:
- Su-ning Chen, M.D.
- 電話番号:+8613814881746
- メール:chensuning@sina.com
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-
参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
コホートと介入
グループ/コホート |
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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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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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2-year rate of RFS
時間枠: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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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OS
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Pre-/post-transplant MRD dynamics
時間枠: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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協力者と研究者
捜査官
- 主任研究者:Su-ning Chen, M.D.、The First Affiliated Hospital of Soochow University
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- menin inhibitors maintenance
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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