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

2026년 9월 17일 업데이트: 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.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

10

단계

  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

  • 이름: Mark C Poznansky, MD, PhD
  • 전화번호: 617-724-6375
  • 이메일: mpoznansky@mgb.org

연구 연락처 백업

연구 장소

  • 미국
    • Massachusetts
      • Boston, Massachusetts, 미국, 02114
        • Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital
        • 연락하다:
        • 수석 연구원:
          • James D Berry, MD, MPH
        • 부수사관:
          • Kellen Quigg, MD, MS

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
생물학적: B cell infusion

infusion of haploidentical donor CD19+ B cells

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Infusion associated adverse events of special interest
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Mark Poznansky

협력자

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

수사관

  • 수석 연구원: James D Berry, MD, MPH, Massachusetts General Hospital

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2027년 9월 1일

기본 완료 (추정된)

2030년 1월 1일

연구 완료 (추정된)

2030년 1월 1일

연구 등록 날짜

최초 제출

2026년 9월 11일

QC 기준을 충족하는 최초 제출

2026년 9월 17일

처음 게시됨 (실제)

2026년 9월 24일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 24일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 17일

마지막으로 확인됨

2026년 9월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • VICBcellALSTrial

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

미정

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다