Cytotoxic T Lymphocytes in Treating Patients With Malignancies With BK and/or JC Virus

Official title

Phase II Study Assessing the Effect of BK Specific CTL Lines Generated by Ex Vivo Expansion in Patients With BK Virus Infection and JC Virus Infection

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.

Detailed 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.

Interventions

• Biological Allogeneic BK-specific Cytotoxic T-lymphocytes
  Given IV
• Other Laboratory Biomarker Analysis
  Correlative studies

Primary outcome measures

• Response, defined as response (R) = (best response [R1] or second best response [R2]) [Time frame: Up to 56 days]
• Incidence of acute graft-versus-host disease (GVHD) [Time frame: Within 28 days of the last dose of cytotoxic T lymphocytes (CTLs)]
• Incidence of adverse events [Time frame: Up to day 100]

Secondary outcome measures (2)

• Overall survival [Time frame: Up to 12 months]
• Glomerular filtration rate [Time frame: Up to 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• M D Anderson Cancer Center — Houston

Publications

• Olson A, Li Y, Marin D, Thall PF, Bassett RL, Barnett M, Basar R, Banerjee PP, Kleiman TA, Chen M, Rexer J, Wintermark M, Choi J, Learned K, Kaur I, Sylejmani M, Abueg G, Chemaly RF, Mulanovich V, Shrestha R, Uprety N, Castro KM, Daher M, Galvan IM, Washington D, Champlin RE, Shpall EJ, Rezvani K. Treatment of Progressive Multifocal Leukoencephalopathy with Third-Party Allogeneic BK Virus T Cells. PMID 42402341
• Olson A, Lin R, Marin D, Rafei H, Bdaiwi MH, Thall PF, Basar R, Abudayyeh A, Banerjee P, Aung FM, Kaur I, Abueg G, Rao S, Chemaly R, Mulanovich V, Al-Atrash G, Alousi AM, Andersson BS, Anderlini P, Bashir Q, Castro KM, Daher M, Galvan IM, Hosing C, Im JS, Jones RB, Kebriaei P, Khouri I, Mehta R, Molldrem J, Nieto Y, Oran B, Popat U, Qazilbash M, Rondon G, Saini N, Spencer B, Srour S, Washington D, PMID 33929874
• Muftuoglu M, Olson A, Marin D, Ahmed S, Mulanovich V, Tummala S, Chi TL, Ferrajoli A, Kaur I, Li L, Champlin R, Shpall EJ, Rezvani K. Allogeneic BK Virus-Specific T Cells for Progressive Multifocal Leukoencephalopathy. N Engl J Med. 2018 Oct 11;379(15):1443-1451. doi: 10.1056/NEJMoa1801540. PMID 30304652

Identifiers

NCT: NCT02479698 · 2014-0279 · NCI-2015-01264 · 2014-0279

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗