Expansion of Virus-Specific Lymphocytes for Cell Therapy

NCT06011486 | Recruiting Phase 1 DMC

• 1 other identifier: U1111-1226-7367
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Infections and reactivation of human cytomegalovirus (CMV), adenovirus, Epstein-barr and polyoma virus infections are frequent causes of morbidity and mortality and are a source of serious complications in patients undergoing allogeneic bone marrow transplantation. In this project we will prepare specific T lymphocytes from blood donor, select cells CMV-specific by interferon gamma capture and treat patients with CMV viral infections. These cells will be used as antiviral therapy in transplanted patients whom do not respond to conventional therapies or in patients whose conventional therapy may be toxic in the context of transplantation. In this context, CMV reactivation can lead to serious complications in patients, such as irreversible neurological changes, pulmonary, gastrointestinal and ophthalmologic complications, among others, in addition to prolonged hospitalizations, leading to significant morbidity and mortality , both in the health sector public as private. This project may represent an important therapeutic modality using cell of the shelf as a source of therapy for different patients and contributing to reduced morbidity / mortality after transplantation, as well as a reduction in the hospitalization period.

Conditions

CMV Viremia; CMV

Outcome Measures

Primary Outcomes (4)

• Number of patients with immediate infusion reactions

  Safety of cytotoxic T cell (CTL) based on patients with grade 3 immediate adverse events that are at least possibly related to the CTL infusion within 3 hours of the CTL infusion, using the grade as follows: Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe with Life-threatening consequences.

  3 hours

• Development of Acute graft versus host disease (GvHD)

  Number of Patients that present Acute GvHD Grades III-IV \[ Time Frame: 6 weeks\] Safety of cytotoxic T Cell (CTL) will be based on patients with acute GvHD grades III-IV within 6 weeks after the last dose of CTL. Acute GVHD grading will be performed according to NIH criteria (1). Grade 0 represents no acute GvHD. Grade 4 represents the most severe acute GvHD. 1-Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, et al. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10.

  6 weeks

• Development of Non-Hematological Adverse events

  Number of Patients With Grades 3 Non-hematologic Adverse Events Related to the T Cell Product \[ Time Frame: 6 weeks \] Safety of VSTs based on patients with grade 3 non-hematologic adverse events that are at least possibly related to the CTL infusion within 6 weeks of the last CTL dose, using the grade as follows: Grade 1 Mild; asymptomatic or mild symptoms. Grade 2 Moderate symptoms. Grade 3 Severe with Life-threatening consequences.

  6 weeks

• Risk for chronic GVHD [ Time Frame: At 6 and12 months post CTL infusion ]

  Survival analysis method will be applied. Time to chronic GVHD will be defined from time of the last CTL infusion to the onset of chronic GVHD, or the last clinical assessment date if no chronic GVHD. Cumulative incidence of chronic GVHD at 6 and 12 months will be estimated.

  6 to 12 montas

Secondary Outcomes (3)

• Antiviral activity defined as response to viral load [ Time Frame: 6 weeks ]

  6 weeks

• Rate of anti-CMV response improvement in the peripheral blood of participants [ Time Frame: 6 weeks ]

  6 weeks

• Clinical response to CTL infusions [ Time Frame: At 6 weeks and 3 months ]

  6 weeks and 3 month

Study Arms (1)

Lymphocyte infusion

EXPERIMENTAL

Patients with CMV disease or reactivation will be included for receiving donor-CMV-specific cells

Combination Product: Lymphocyte infusion (ImmuneCellVir-I)

Interventions

Lymphocyte infusion (ImmuneCellVir-I) COMBINATION_PRODUCT

Infusion of donor CMV specific cells into patients eligible to the trial

Also known as: CMV-specific cells infusion

Lymphocyte infusion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to provide signed informed consent.
• Must be between 18 and 75 years old at the time of signing the consent form
• Having undergone allogeneic hematopoietic stem cell transplantation (related, unrelated, haploidentical or cord blood transplant)
• Negative pregnancy test for women of childbearing age (non-fertile age defined as post-menopausal over one year, or surgically sterilized); Acceptance of the use of contraceptive methods by sexually active men and women of childbearing age;
• Present with clinically significant CMV infection and one of the following conditions:
• Refractory CMV infection, defined as over a 1log increase in blood or plasma CMV copies number after 2 weeks of treatment with appropriate anti-CMV medication (treatment with ganciclovir, valganciclovir, or foscarnet)
• Probable refractory CMV infection, defined as persistence of CMV DNA in blood or plasma at the same level or under 1 log increase after 2 weeks of treatment with appropriate anti-CMV medication (treatment with ganciclovir, valganciclovir, or foscarnet)
• Presence of resistant CMV, defined by the presence of a known genetic mutation that reduces susceptibility to one or more antiviral medications
• Refractory CMV disease, defined as worsening of signs and symptoms and/or progression to CMV disease after 2 weeks of appropriate antiviral therapy
• Restrictions or complications related to conventional therapy, which make it impossible to carry out conventional drug treatment defined as cytopenias with neutrophils under 1000 per microliter, platelets under 100,000 per microliter related to the use of ganciclovir or valganciclovir and nephrotoxicity with an increase of 1.5 times in the baseline creatinine with the use of foscavir.

You may not qualify if:

• Patients who do not agree to participate in the study or sign the consent form
• Patients reporting allergy to murine antibodies or iron-dextran
• Patients with grade 3 or 4 graft versus host disease/graft versus host disease in activity/treatment
• Pregnant or lactating patients
• Patients with uncontrolled bacterial and/or fungal infections

Sponsors & Collaborators

• Hospital Israelita Albert Einstein: lead

Study Sites (1)

Hospital Israelita Albert Einstein

São Paulo, São Paulo, 05653000, Brazil

RECRUITING

Study Officials

• Nelson Hamerschlak, MD, PhD

  Hospital Israelita Albert Einstein

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nelson C Hamerschlak, MD, PhD

CONTACT

+5511999614340; hamer@einstein.br

Luciana C Marti, PhD

CONTACT

+5511983716733; luciana.marti@einstein.br

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2023
• First Posted: August 25, 2023
• Study Start: June 10, 2024
• Primary Completion: June 10, 2025
• Study Completion (Estimated): June 10, 2026
• Last Updated: October 24, 2024

Record last verified: 2024-09

Locations

BR (1)