Overview
This phase II trial studies how well donor cytotoxic T lymphocytes work in treating patients with malignancies with BK and/or JC virus. Cytotoxic T lymphocytes are made from donated blood cells that are grown in the laboratory and are designed to kill viruses that can cause infections in transplant patients and may be an effective treatment in patients with malignancies with BK and/or JC virus.
Description
PRIMARY OBJECTIVE:
I. To assess the efficacy, feasibility and safety of administering most closely human leukocyte antigen (HLA)-matched BK specific cytotoxic T lymphocyte (CTL) lines (BK-CTLs) generated by ex vivo expansion to mediate antiviral activity in patients with any type of malignancies, and/or human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDs), and/or history of solid organ transplant with BK and JC infections.
SECONDARY OBJECTIVE:
I. To assess the persistence of the administered BK-CTLs generated by ex vivo expansion in patients with any type of malignancies, and/or HIV/AIDs, and/or history of solid organ transplant with BK and JC infections.
- OUTLINE
Patients receive allogeneic BK-specific cytotoxic T-lymphocytes intravenously (IV) over 30 minutes. Patients achieving partial response, stable disease, or progressive disease are eligible for 7 additional infusions of CTL occurring at least 2 weeks after the previous CTL infusion if they meet the eligibility criteria for subsequent therapy.
After completion of study treatment, patients are followed up periodically for 12 months.
Eligibility
Inclusion Criteria:
- Patients ≥ 2 years. English and non-English speaking patients are eligible.
- Immunocompromised patients; and/or Non-immunocompromised patients with PML/JC virus Encephalitis; and/or patients with any type of malignancies; and/or HIV/AIDs; and/or history of solid organ transplant; and/or Merkel polyoma-virus related Merkel cell tumor(s) with measurable disease on imaging per RECIST criteria.
- Patients with microscopic hematuria OR biopsy proven BK nephritis and urine or blood PCR positive for BK virus and/or JC viral encephalitis and/or JC end-organ disease and/or polyomavirus.
- Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day of prednisone.
- Patients who are currently receiving treatment with cidofovir, leflunomide, or other antiviral therapy with no response, will be eligible for CTL infusion.
- Written informed consent and/or signed assent from patient, parent or guardian. Patients with cognitive impairments are eligible.
- Negative pregnancy test in female patients of childbearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.
- Patients enrolled on this study may be enrolled on other IND studies at the discretion of the PI.
- Patients may be re-enrolled in the protocol should the infection re-occur, provided they meet all the other eligibility criteria at the moment of re-enrollment.
Exclusion Criteria:
- Patients receiving prednisone \> 0.5 mg/kg/day at time of enrollment, or have received ATG within 14 days or have received donor lymphocyte infusion (DLI) or Campath within 28 days of enrollment.
- Patients with other uncontrolled infections (except HIV/AIDS). 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 active acute (GVHD) grades II-IV
