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

NCT ID: NCT02479698

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-23
• Study Completion Date: 2027-07-31

Brief Summary

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.

Conditions

Acquired Immunodeficiency Syndrome; BK Virus Infection; Human Immunodeficiency Virus; JC Virus Infection; Malignant Neoplasm; Merkel Cell Carcinoma; Merkel Cell Polyomavirus Infection; Viral Encephalitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (BK-specific cytotoxic T lymphocytes)

Patients receive allogeneic BK-specific cytotoxic T-lymphocytes IV over 30 minutes. Patients achieving partial response, stable disease, or progressive disease are eligible for 19 additional infusions of CTL occurring at least 2 weeks after the previous CTL infusion if they meet the eligibility criteria for subsequent therapy.

Group Type: EXPERIMENTAL

Allogeneic BK-specific Cytotoxic T-lymphocytes

Intervention Type: BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Allogeneic BK-specific Cytotoxic T-lymphocytes

Given IV

Intervention Type: BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Allogeneic BK-CTLs; Allogeneic BK-specific CTLs

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amanda Olson

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Amanda L. Olson, MD

Role: CONTACT

ALOlson@mdanderson.org

713-792-8750

Facility Contacts

Amanda Olson

Role: primary

713-792-8750

References

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, Barnett M, Champlin RE, Shpall EJ, Rezvani K. Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation. J Clin Oncol. 2021 Aug 20;39(24):2710-2719. doi: 10.1200/JCO.20.02608. Epub 2021 Apr 30.

Reference Type: DERIVED

PMID: 33929874 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30304652 (View on PubMed)

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2015-01264

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-0279

Identifier Type: OTHER

Identifier Source: secondary_id

2014-0279

Identifier Type: -

Identifier Source: org_study_id