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Donor CMV Specific CTLs in Treating CMV Reactivation or Infection in Patients who have Undergone Stem Cell Transplant or Solid Organ Transplant

Trial Status: Active

This phase I trial studies the side effects and how well allogeneic cytomegalovirus-specific cytotoxic T lymphocytes (donor cytomegalovirus [CMV] specific cytotoxic T-lymphocytes [CTLs]) work in treating CMV reactivation or infection in patients who have undergone stem cell transplant or solid organ transplant. White blood cells from donors may be able to kill viral cells in patients with cytomegalovirus that has come back after a stem cell or solid organ transplant.

Inclusion Criteria

  • Patients must have received solid organ transplant (renal, heart, lung, liver, pancreas, small bowel, multi-visceral) or have received allogeneic hematopoietic stem cell transplant (bone marrow, peripheral blood [PB] or umbilical cord blood [UCB]) and be > 30 days post-transplant at the time of screening
  • Must have documented CMV refractory disease with viremia as detected by quantitative polymerase chain reaction (PCR) (> 500 IU/ml) in the peripheral blood requiring treatment
  • If not meeting CMV refractory definition, must be defined as high risk for antiviral failure due to history of recurrent CMV reactivations, active CMV disease, recently started on increased immunosuppressants for graft versus host disease (GVHD) in setting of positive CMV PCR or unable to tolerate antiviral treatment due renal toxicity, bone marrow suppression, transfusion dependent anemia and thrombocytopenia or neutropenia requiring growth factor support or other related organ injury
  • No active acute (a)GVHD or chronic (c)GVHD. Stable GVHD is permitted as long as patients are on stable dose steroids of less than or equal to 0.5 mg/kg/day of prednisone or steroid equivalent
  • Successful primary engraftment (chimerisms CD33 >= 70%, CD3 >= 50%) without secondary graft failure
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Available CMV seropositive haploidentical donor who is without evidence of infection that would otherwise preclude donation
  • Negative pregnancy test in female patients if applicable (childbearing potential, has not received a full-intensity conditioning regimen
  • Written informed consent and/or signed assent line from patient, parent or guardian
  • DONOR
  • Human leukocyte antigen (HLA)-haploidentical to the patient as determined by institutional standards
  • CMV seropositive, defined as detection of serum CMV immunoglobulin G (IgG)
  • Weight > 110 lbs
  • Meet donor eligibility or suitability according to institutional standards. If the donor is deemed ineligible according to Foundation for the Accreditation of Cellular Therapy (FACT) standards, but is suitable for donation per institutional standards, the donor will be eligible for the protocol

Exclusion Criteria

  • Receipt of anti-thymocyte globulin (ATG), alemtuzumab, cytoxan, pentostatin or other T-cell depleting antibodies within 28 days of screening for enrollment
  • Receiving > 0.5mg/kg/day of prednisone or steroid equivalent at the time of enrollment
  • Evidence of uncontrolled infection (except CMV) as follows: * Bacterial infections - patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment * Fungal infections - patients must be receiving definitive systemic anti-fungal therapy and evidence of response/stabilization on therapy for 1 week prior to enrollment * Progressing infection is defined as hemodynamic instability attributable to sepsis, or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
  • Receipt of donor lymphocyte infusion (DLI) within 28 days of projected CMV specific T cell infusion
  • Active acute GVHD grades >= II-IV
  • Evidence of acute solid organ graft rejection as determined by treating physician
  • Active and uncontrolled relapse of malignancy

Ohio

Columbus
Nationwide Children's Hospital
Status: ACTIVE
Contact: Christopher P Ouellette
Phone: 614-722-4452
Ohio State University Comprehensive Cancer Center
Status: ACTIVE
Contact: Sumithira Vasu
Phone: 614-293-3196

PRIMARY OBJECTIVE

I. Assess the safety and feasibility of administering CMV specific-CTLs from haploidentical donors to both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) with CMV infection that is refractory to standard therapy.

OUTLINE:

Patients receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes intravenously (IV).

After completion of study treatment, participants are followed up at 1 year.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Ohio State University Comprehensive Cancer Center

Principal Investigator
Sumithira Vasu

  • Primary ID OSU-17199
  • Secondary IDs NCI-2018-01412, 2018C0105
  • Clinicaltrials.gov ID NCT03665675