Dexamethasone, Intravenous Injection of Human Immunoglobulin, and Increased Infusion of Mononuclear Cells to Reduce Donor Specific Antibodies in Haploidentical Hematopoietic Stem Cell Transplantation
Dexamethasone, Intravenous Injection of Human Immunoglobulin, and Increased Infusion of Mononuclear Cells to Reduce Donor Specific Antibodies in Haploid Hematopoietic Stem Cell Transplantation: a Prospective, Multicenter Study
This study tests whether a combination of three treatments - dexamethasone (a steroid), intravenous immunoglobulin (IVIG, a protein that helps the immune system), and an extra dose of donor mononuclear cells - can safely lower harmful antibodies called donor-specific antibodies (DSA) in patients who need a stem cell transplant from a half-matched (haploidentical) family donor.
In these transplants, DSA are antibodies made by the patient's own body that attack the donor's stem cells. If DSA levels are high, the transplant is more likely to fail - the donor cells may not "take" (engraft). Currently, there is no single, simple, and reliable way to reduce DSA, and many existing methods have drawbacks.
Based on the investigators' earlier experience in 11 patients, this three-part approach seemed to work well. All patients successfully engrafted, and DSA levels dropped quickly. Now the study team want to confirm these results in a larger, prospective, multicenter study.
The investigators plan to enroll 60 patients aged 18-65 with blood cancers or other blood disorders who need a haploidentical transplant, have DSA levels above 500 MFI (a measure of antibody strength), and have no other suitable donor available. Participants will receive:
- Dexamethasone (25 mg/m²) for 4 days before transplant,
- IVIG (1 g/kg) one day before transplant,
- Extra mononuclear cells on transplant day - the extra amount depends on how high their DSA level is (low, medium, or high).
The main goal is to see how many patients have primary graft failure (when the donor cells never engraft). The study team will also measure how long it takes for blood counts to recover, rates of graft-versus-host disease, survival, and side effects. All participants will be followed for 1 year.
This study will help the investigators find out whether this combination is a safe, simple, and effective way to improve transplant success for patients with DSA who have no other donor options.
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Sanbin Wang
- 電話番号：+8613187424131
- メール：sanbin1011@163.com
研究連絡先のバックアップ
- 名前：Xi Xiong
- 電話番号：+8615987422538
- メール：15987422538@163.com
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Diagnosis of benign or malignant hematological diseases (including leukemia, lymphoma, thalassemia, aplastic anemia, myelodysplastic syndromes, etc.) confirmed by NCCN guidelines, and determined by the investigator to require allogeneic hematopoietic stem cell transplantation.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3.
- Donor-specific antibody (DSA) mean fluorescence intensity (MFI) > 500.
- Age between 18 and 65 years (age limits are also captured separately in the eligibility module).
- Body weight between 40 kg and 100 kg.
- No other suitable donor available (i.e., no DSA-negative related donor or unrelated donor).
Exclusion Criteria:
- Patients unsuitable for transplantation or without willingness to undergo transplantation, or diagnosed with non-hematological diseases.
- Estimated life expectancy < 1 month.
- Known allergy to any drug or intervention used in the study regimen.
- Pregnancy, lactation, active severe infection, or severe major organ dysfunction.
- Severe psychiatric or neurological disorders that may affect the ability to provide informed consent and/or to report adverse events or comply with observation.
- Refusal or inability to sign the informed consent form.
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
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Triple Therapy to Reduce DSA in Haploidentical HSCT: A Prospective Multicenter Study
Participants receive dexamethasone (25 mg/m² × 4 days) and intravenous immunoglobulin (1 g/kg) prior to haploidentical hematopoietic stem cell transplantation, plus an additional dose of donor mononuclear cells on transplant day.
The additional dose is stratified by baseline DSA MFI level: ≤5000: +2±2×10⁸/kg; 5000-10000: +4±2×10⁸/kg; >10000: +6±2×10⁸/kg.
|
1 g/kg intravenously on day -1 prior to transplant.
25 mg/m² intravenously for 4 days prior to transplant (days -4 to -1).
Additional donor MNCs infused on day 0. Dose stratified by baseline DSA MFI level: ≤5000: +2±2×10⁸/kg; 5000-10000: +4±2×10⁸/kg; >10000: +6±2×10⁸/kg.
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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 |
時間枠 |
|---|---|
|
Primary Graft Failure (PGF)
時間枠：Day +28 post-transplant
|
Day +28 post-transplant
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Neutrophil and Platelet Engraftment Time
時間枠：Up to 28 days post-transplant
|
Up to 28 days post-transplant
|
|
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Dynamic Changes in Donor-Specific Antibody (DSA) MFI Levels
時間枠：Pre-transplant (day -14 to -1) through day +22 post-transplant
|
Pre-transplant (day -14 to -1) through day +22 post-transplant
|
|
|
Incidence of Acute and Chronic Graft-Versus-Host Disease
時間枠：Up to 1 year post-transplant
|
Cumulative incidence of acute GVHD (aGVHD) graded by standard criteria within 100 days post-transplant, and chronic GVHD (cGVHD) graded by NIH consensus criteria from day +100 through 1 year post-transplant.
|
Up to 1 year post-transplant
|
|
Overall Survival and Disease-Free Survival
時間枠：Up to 1 year post-transplant
|
Overall survival (OS) defined as time from transplant to death from any cause.
Disease-free survival (DFS) defined as time from transplant to relapse, progression, or death from any cause.
Estimated using Kaplan-Meier method at 1 year.
|
Up to 1 year post-transplant
|
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Incidence of Adverse Events
時間枠：Up to 1 year post-transplant
|
Incidence of infectious complications (bacterial, viral, fungal), bleeding events, and other treatment-emergent adverse events.
Graded according to CTCAE criteria.
|
Up to 1 year post-transplant
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
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
追加の関連 MeSH 用語
- 骨髄不全疾患
- 新生物
- 遺伝性疾患、先天性疾患
- 免疫系疾患
- 組織型別の新生物
- 血液疾患
- リンパ疾患
- リンパ増殖性疾患
- 免疫増殖性疾患
- 骨髄疾患
- 貧血、溶血性、先天性
- 貧血、溶血
- 貧血
- 異常ヘモグロビン症
- 先天性、遺伝性、および新生児の疾患と異常
- ヘミックおよびリンパ疾患
- 白血病
- リンパ腫
- 骨髄異形成症候群
- サラセミア
- 貧血、再生不良
- アミノ酸、ペプチド、およびタンパク質
- タンパク質
- 多環式化合物
- 抗体
- 免疫グロブリン
- 免疫タンパク質
- 血液タンパク質
- 血清グロブリン
- グロブリン
- 妊娠
- 妊娠
- ステロイド
- 融合リング化合物
- ステロイド、フッ素化
- 妊娠症
- 免疫グロブリンアイソタイプ
- 免疫グロブリンG
- デキサメタゾン
- 免疫グロブリン、静脈内投与
その他の研究ID番号
- KM-10
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
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米国FDA規制機器製品の研究
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