Treatment of BK Virus Infection With CTL Cells in Immunocompromised Transplant Patients

Официальное название

A Pilot Study in the Treatment of BK Virus Infection With Cytotoxic T Cells in Immunocompromised Transplant Patients

Обзор

This is a pilot study using cytotoxic T lymphocytes (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Gamma-capture system will be effective in decreasing specific viral load in patients with BK virus viremia and BK virus-associated symptoms post-allogeneic hematopoietic stem cell transplantation (HSCT), renal transplantation, and chemotherapy.

Подробное описание

This open-label, single-arm clinical trial will assess the safety and efficacy of BK virus-specific CTLs isolated from whole blood or leukapheresis products. The BK virus -specific CTLs will be generated automatically by the CliniMACS® Prodigy using the CliniMACS Cytokine Capture System (IFNgamma) after incubation with MACS GMP PepTivator® Peptide Pools of BKV VP1 and BKV LT.

Вмешательства

• Биопрепарат BK-virus specific CTLs
  HLA Matched Related Donors: BK-virus specific CTLs (2.5 x 104 CD3/kg) infused intravenously on day 0 and may be additionally reinfused at a minimum of every two weeks (depending on safety and efficacy) for a maximum of five total infusions (maximum 12.5 x 104 CD3/kg). HLA Mismatched Related Donors: BK-virus specific CTLs (0.5x104 CD3/kg) infused intravenously on day 0 and may additionally be reinfused at a minimum of every two weeks (depending on safety and efficacy) for a maximum of five total

Первичные конечные точки

• Number of participants with Grade III-IV acute GVHD [Срок оценки: Up to 8 weeks after last BK-CTL infusion]
• Number of patients with undetectable BK viral load [Срок оценки: 12 weeks after first BK-CTL infusion]

Критерии участия

Критерии включения

Patient Eligibility

• Patients with symptoms of cystitis and elevated BK virus DNA by screening PCR as above (section 4) post allogeneic HSCT, post chemotherapy

• Symptoms of cystitis may include: hematuria (microscopic or gross), pain with urination, frequency, bladder spasms.
• Patient may be otherwise treated for cystitis as per local institutional standards. Such treatments may include hydration, antiviral medications, or surgical intervention as deemed appropriate by treating physician.
• Consent: Written informed consent given (by patient or legal representative) prior to any study-related procedures.
• Performance Status > 30% (Lansky < 16 yrs and Karnofsky > 16 yrs)
• Age: 0.1 to 25 years
• Females of childbearing potential with a negative urine pregnancy test.

Donor Eligibility

• Related donor available with a T-cell response to the BK-virus MACS® PepTivator® antigen(s).

• Original allogeneic donor if available, IgG positive for BKV or confirmatory testing to respond to BKV MACS Peptivator®.
• Third Party Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party allogeneic donor (family donor > 1 HLA A, B, DR match to recipient) with a T-cell response to the BK MACS® PepTivator.

AND

• Allogeneic donor disease screening is complete similar to hematopoietic stem cell donors (Appendix 1).

AND

• Obtained informed consents by donor or donor legally authorized representative prior to donor collection.

Критерии исключения

Patient exclusion criteria:

A patient meeting any of the following criteria is not eligible for the present study:

• Patient with acute GVHD > grade 2 or extensive chronic GVHD at the time of BK Virus CTL infusion
• Patient receiving steroids (>0.5 mg/kg prednisone equivalent) at the time of BK Virus CTL infusion or within 3 days of planned infusion.
• Thymoglobulin (ATG), campath or T cell immunosuppressive monoclonal antibodies within 30 days
• Patient with poor performance status determined by Karnofsky (patients >16 years) or Lansky (patients ≤16 years) score ≤30%
• Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory BK virus infection.
• Any medical condition which could compromise participation in the study according to the investigator's assessment
• Known HIV infection
• Female patient of childbearing age who is pregnant or breast-feeding or not willing to use an effective method of birth control during study treatment.
• Known hypersensitivity to iron dextran
• Patients unwilling or unable to comply with the protocol or unable to give informed consent.
• Known human anti-mouse antibodies

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

США · 1 центр

• Children's Hospital of Philadelphia — Philadelphia

Идентификаторы

NCT: NCT04293042 · 19-016545

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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