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Evaluation of Donor-Derived B Cell Infusions in Patients With Amyotrophic Lateral Sclerosis (ALS)

2026年9月17日 更新者：Mark Poznansky

Evaluation of Haploidentical, Donor-Derived B Lymphocyte Infusions in Patients With Amyotrophic Lateral Sclerosis

This study is testing whether giving people with ALS specially matched immune cells called B cells from a related donor is safe. Up to 10 participants will each receive two B cell infusions at least 60 days apart. The main goals are to watch closely for side effects, see whether the participant's immune system rejects the donor cells, and determine whether this treatment should be studied further in people with ALS. The first three participants will receive the infusions in the hospital with extra safety spacing between participants; if those infusions appear safe, the remaining participants may receive them in an outpatient setting.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

This is a phase 1, non-randomized, open-label study to assess the safety and pharmacokinetics of up to 2 doses of donor B cells. Up to 10 recipients will each receive 2 infusions of donor B cells at doses of ≥ 2.0 x 10^8 and ≤ 1.0 x 10^9 donor B cells delivered at least 60 days apart. The first three participants will receive infusions as inpatients in a staggered fashion 30 days apart. After completion of a 30-day observation of the third participant after the second infusion, study investigators will determine whether the infusions are safe and well-tolerated and that there are no indications of significant immune rejection of the donor B cells. In such a case the remaining participants will receive 2 infusions in an outpatient setting with no mandatory staggering interval. Each participant will be followed for six months after the second infusion.

Donors. Each subject will be consented along with a relative meeting the HLA matching requirements to serve as a donor. The patient and potential donor will be HLA (A, B and DR- B1) tested and the potential donor will be a haploidentical match to the recipient, will have cleared all medical and infectious diseases screening tests, and will have agreed to be the B cell donor for this study. Each donor will undergo one or more leukapheresis procedures each yielding up to 1.5 mL of a concentrated white cell fraction. Purified B cells will be derived from these cells for a target final yield of between 2.0 x 108 and 1.0 x 109 B cells. Purified donor B cells will be stored in liquid nitrogen and thawed at bedside for infusion into participant.

Recipients. Prior to infusion, each enrolled subject will have a pre-infusion visit (study Day -50 to -40) where medical history will be taken, vitals and ALS-related measurements will be taken and a blood sample drawn to establish baseline blood counts, chemistry, and immunologic profile.

Treatment. All participants will receive up to 2 infusions of ≥ 2.0 x 10^8 and ≤ 1.0 x 10^9 donor B cells with the second infusion no less than 60 days after the first infusion. Participants will receive infusions with no preparatory treatment. Donor B cells in a concentration of 1.0 x 10^7 donor B cells/mL in a volume of up to 100 mL will be delivered over a 2-hour period through a peripheral line pre-incubated with a 4% solution of human serum albumin.

Evaluation. The first three participants will receive infusions as inpatients to carefully monitor responses to infusions for up to 24 hours. These participants will be staggered 30 days apart. If infusions of inpatient participants appear to be well tolerated and safe, the remaining participants will receive infusions as outpatients with no staggering.

Safety monitoring will include periodic measurement of vital signs and specific blood tests, monitoring of changes in medical history, reports of AEs, evaluation of ALS status through ALSFRS-R and grip strength, and assessment of Columbia Suicide Severity Rating Scale.

Blood tests will be taken periodically to monitor for changes in CBC, including ESR and CRP, and a metabolic panel that includes an expanded range of kidney function tests as well as ferritin. Study investigators will evaluate blood markers of immune rejection at time points up to the first four weeks after each infusion.

During the study, blood tests will be taken periodically to monitor other immunologic markers including flow cytometry using an established antibody panel developed for the previously-conducted expanded access studies.

研究の種類

介入

入学 (推定)

10

段階

  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

  • 名前：Mark C Poznansky, MD, PhD
  • 電話番号：617-724-6375
  • メール：mpoznansky@mgb.org

研究連絡先のバックアップ

研究場所

  • アメリカ
    • Massachusetts
      • Boston、Massachusetts、アメリカ、02114
        • Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital
        • コンタクト：
        • 主任研究者：
          • James D Berry, MD, MPH
        • 副調査官：
          • Kellen Quigg, MD, MS

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年～70年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  1. Confirmed diagnosis of ALS that meets the revised El Escorial criteria for probable lab-supported, probable, or definite ALS.

  2. Age 18-70 years.

  3. Vital capacity of >65%.

  4. ALSFRS-R score of >30.

  5. Absence of clinically important abnormalities on screening labs, including but not limited to ALT/AST < 3x ULN, Bilirubin <1.5x ULN (unless there is documented history of Gilbert's disease), serum Cr < 1.5x ULN, WBC > 3.5, HCT >33, Plts > 120.

  6. Negative tests for HIV, HepB sAg, HCV.

  7. Available potential donor who must be a haploidentical match to the recipient and agree to be the B cell donor for this study.

    • Note: Participants are eligible if they are taking any, all, or none of the following: riluzole, edaravone, and/or high-dose methylcobalamine; and the start date of these medications are at least 30 days prior to the baseline visit.

Exclusion Criteria:

  1. Unable or unwilling to comply with protocol requirements.

  2. Known current or history of recurrent bacterial, viral, fungal, mycobacterial, or other opportunistic infection.

  3. Use of tofersen (Qalsody).

  4. Use of Rituximab (Rituxan), Ocrelizumab (Ocrevus), Ofatumumab (Kesimpta, Arzerra), Epratuzumab (LymphoCide), Belimumab (Benlysta), MEDI-551, or other anti-CD20, anti-CD19, or anti-CD22 antibodies.

  5. Use of Atacicpet or other BlyS or APRIL inhibitors.

  6. Use of Chimeric antigen-receptor T cells targeting CD19 or CD20, including tisagenlecleucel (Kymriah), Aaxicabtagene ciloleucel (Yescarta), brexucabtagene autoleucel (Tecartus), and lisocabtagene maraleucel (Breyanzi).

  7. Additional active neurological disease that could confound the participant's ALS symptoms.

  8. Major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening.

  9. Immunization with live-attenuated vaccines within 4 weeks of screening. Study participant must agree to forgo live-attenuated vaccines throughout the study.

  10. Chronic immunosuppression (any chronic immunosuppressive immunotherapy including daily oral steroid use > 6 months).

  11. Other active autoimmune disease except psoriasis or hypothyroidism.

  12. Active malignancy (excluding skin cancer other than melanoma) within 5 years.

  13. History of any of the following: cardiac insufficiency (defined as New York Heart Association III/IV), unstable ischemic heart disease, uncontrolled cardiac arrhythmias, or uncontrolled hypertension (defined as systolic blood pressure >170 mmHg or diastolic blood pressure >110 mmHg).

  14. Unstable cardiac, renal, hepatic, endocrine, pulmonary or hematologic disease, at the discretion of the PI.

  15. Anything that, in the opinion of the PI, would place the participant at increased risk or preclude the participant's full compliance with or the completion of the study.

  16. Participant unwilling to practice contraception for the duration of the study. Men and women of childbearing potential (WOCBP) should use an approved method of birth control and agree to continue to use this method for the duration of the study.

    Acceptable methods of contraception include abstinence, female participants/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only) (e.g., diaphragm, cervical cap, male condom, and female condom and spermicidal foam, sponges, and film), female participant's/partner's use of an intrauterine device (IUD), or if the female participant/partner is surgically sterile (e.g., bilateral tubal ligation, hysterectomy) or two years postmenopausal at time of screening. All male participants/partners (excluding men who have been sterilized) must agree to consistently and correctly use a condom for duration of the study. In addition, participants may not donate sperm for the duration of the study.

  17. Participation in another interventional trial or use of an experimental ALS product with an ongoing clinical development program in an expanded access program, compassionate use program or through practitioner prescription. Over the counter medications are acceptable, as are standard of care ALS medications.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

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：ALS patients receiving infusions of haploidentical donor B cells

ALS patients receiving infusions of haploidentical donor B cells between 200 million and 1 billion cells per infusion with the second infusion 60 days after the first.
生物学的：B cell infusion

infusion of haploidentical donor CD19+ B cells

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
Infusion associated adverse events of special interest
時間枠：Up to 6 months after 2nd infusion

Safety and tolerability of up to 2 infusions of donor B cells at individual doses of between 2.0 x 10^8 and 1.0 x 10^9 donor B cells defined by:

  • Incidence of all AEs, as defined for the 30-day time point, at 60 days.
  • Incidence of Treatment Emergent Serious Adverse Events (TE-SAEs) at 30 days defined as the composite of graft-versus-host disease, other persistent immunologic abnormalities, bleeding disorders, stroke, myocardial infarction, or death.
Up to 6 months after 2nd infusion
Evidence of host rejection of infused cells
時間枠：Within 4 weeks of 2nd infusion

Donor cell rejection: Indications of immune rejection of B cell infusions defined by changes in specific blood markers and ex vivo cell assays after either the first or second infusion of donor B cells compared to baseline levels of each.
Within 4 weeks of 2nd infusion

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Mark Poznansky

協力者

Dana-Farber Cancer Institute
Massachusetts Eye and Ear Infirmary
Alira Health

捜査官

  • 主任研究者：James D Berry, MD, MPH、Massachusetts General Hospital

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2027年9月1日

一次修了 (推定)

2030年1月1日

研究の完了 (推定)

2030年1月1日

試験登録日

最初に提出

2026年9月11日

QC基準を満たした最初の提出物

2026年9月17日

最初の投稿 (実際)

2026年9月24日

学習記録の更新

投稿された最後の更新 (実際)

2026年9月24日

QC基準を満たした最後の更新が送信されました

2026年9月17日

最終確認日

2026年9月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • VICBcellALSTrial

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?

未定

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

はい

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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