Using donor-derived T cells to treat viral infections after cord blood transplantation
Adoptive Cord Blood ImmunotHerapy Using Expanded Cord Blood T Cells for EBV, CMV, BKV and Adenovirus Reactivation/Infection or ProphylaxiS
This study is testing different doses of donor T cells to see if they can help patients who are at risk of viral infections after receiving a cord blood transplant.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 36 (estimated) |
| Sex | All |
| Sponsor | Children's National Research Institute Academic / other |
| Drugs / interventions | prednisone |
| Locations | 2 sites (Washington D.C., District of Columbia and 1 other locations) |
| Trial ID | NCT03594981 on ClinicalTrials.gov |
What this trial studies
This Phase I-II trial aims to find the optimal intravenous dose of donor-derived cytotoxic T lymphocytes (CTLs) targeting CMV, EBV, BKV, and Adenovirus in patients at risk of reactivation or infection following umbilical cord blood transplantation. A total of 36 patients will be treated in up to 18 cohorts, starting with the lowest dose and escalating based on the EffTox method, which balances efficacy and toxicity. The study will evaluate three specific dose levels to determine the most effective and safe dosage for future treatments.
Who should consider this trial
Good fit: Ideal candidates include pediatric and adult patients with malignant or nonmalignant diseases who are candidates for umbilical cord blood transplantation.
Not a fit: Patients who do not have a matched cord blood unit or those not undergoing transplantation may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly reduce the incidence of viral infections in patients undergoing cord blood transplantation.
How similar studies have performed: Other studies have shown promise in using T cell therapies for viral infections, indicating a potential for success with this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: Inclusion Criteria at the Time of Procurement * Pediatric and adult patients (there are no lower and upper age limits for patients) with malignant or nonmalignant diseases who are candidates for transplant. * Patients must have a CB unit (or units) matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The unit selected for CTL expansion must be either: 1. be cryopreserved in two fractions, with a minimum of 2.5x107 total nucleated cells (TNC) per kg pre-thaw in the fraction which will be used for the primary transplant. The remaining fraction will be used to generate the CTLs to give at day 30 or beyond as described below. OR 2. be cryopreserved with a cell dose that totals \> 3x10e7 TNC per kg pre thaw. On thaw, 20% of the total volume will be used for CTL manufacture to give at day 30 or beyond and the remaining 80% will be used for the primary transplant. 3. For recipients of double CBT, if possible both CB units should be cryopreserved in two fractions and T-cells will be made from both units if possible. Inclusion Criteria at the Time of CTL Infusion * Recipients of at least one unmanipulated cord blood unit as described above (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral/BKV and/or EBV infection or reactivation. * Lansky/Karnofsky scores ≥60 * Absolute neutrophil count (ANC) greater than 500/u * No evidence of GVHD \> Grade II at time of enrollment * Life expectancy \> 30 days * Absence of severe renal disease (Creatinine \< 3x normal for age) * Absence of severe hepatic disease. Direct bilirubin must be \< 3 mg/dl and AST \< 5x upper limit of normal * Patient must be at least 30 days post transplant to be eligible to receive CTL * Written informed consent and/or signed assent line from patient, parent or guardian Exclusion Criteria: Exclusion Criteria at the Time of Procurement * Pregnant or lactating * Patients with active central nervous system disease * Patients with Karnofsky performance status \<70% * Patients with grade 3 or 4 or primary myelofibrosis * Patients with suitable related donors Exclusion Criteria at the Time of CTL Infusion * Pregnant or lactating * Patient on Fi02 of \>60% * Unable to wean steroids to ≤0.5 mg/kg/day prednisone or equivalent * Patients with Grade 3 hyperbilirubinemia * Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia and/or BK viruria/viremia). For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection 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. * Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease * Patients who have received investigational (IND) product within 28 days of screening for CTL infusion under this study
Where this trial is running
Washington D.C., District of Columbia and 1 other locations
- Children's National Health System — Washington D.C., District of Columbia, United States (Recruiting)
- M.D. Anderson Cancer Center (MDACC) — Houston, Texas, United States (Recruiting)
Study contacts
- Study coordinator: Allistair Abraham, MD
- Email: AAbraham@childrensnational.org
- Phone: 202-476-5772
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.