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

17 settembre 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Stimato)

10

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

  • Nome: Mark C Poznansky, MD, PhD
  • Numero di telefono: 617-724-6375
  • Email: mpoznansky@mgb.org

Backup dei contatti dello studio

Luoghi di studio

  • Stati Uniti
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti, 02114
        • Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital
        • Contatto:
        • Investigatore principale:
          • James D Berry, MD, MPH
        • Sub-investigatore:
          • Kellen Quigg, MD, MS

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 70 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Biologico: B cell infusion

infusion of haploidentical donor CD19+ B cells

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Infusion associated adverse events of special interest
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Mark Poznansky

Collaboratori

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

Investigatori

  • Investigatore principale: James D Berry, MD, MPH, Massachusetts General Hospital

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 settembre 2027

Completamento primario (Stimato)

1 gennaio 2030

Completamento dello studio (Stimato)

1 gennaio 2030

Date di iscrizione allo studio

Primo inviato

11 settembre 2026

Primo inviato che soddisfa i criteri di controllo qualità

17 settembre 2026

Primo Inserito (Effettivo)

24 settembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

24 settembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

17 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • VICBcellALSTrial

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

INDECISO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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