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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acquired Immunodeficiency Syndrome; BK Virus Infection; Merkel Cell Carcinoma; Human Immunodeficiency Virus; Malignant Neoplasm; JC Virus Infection; Merkel Cell Polyomavirus Infection; Viral Encephalitis
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Allogeneic BK-specific Cytotoxic T-lymphocytes

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amanda L. Olson, MD; Phone Number: 713-792-8750; Email: ALOlson@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Amanda Olson; Phone Number: 713-792-8750
      • Principal Investigator: Amanda Olson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Patients with microscopic hematuria OR biopsy proven BK nephritis and urine or blood polymerase chain reaction (PCR) positive for BK virus and/or JC viral encephalitis
• 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
• Once patients have completed 6-week safety and efficacy assessments after completion of the last anti-BK CTL infusion, patients will be eligible for enrollment on other supportive care protocols
• Written informed consent from patient and/or signed assent from patient, parent or guardian
• 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

Exclusion Criteria:

• Patients receiving prednisone > 0.5 mg/kg/day at time of enrollment, or have received anti-thymocyte globulin (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 graft-versus-host disease (GVHD) grades II-IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Allogeneic BK-specific Cytotoxic T-lymphocytes; Given IV; Other Names: Allogeneic BK-CTLs; Allogeneic BK-specific CTLs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response, defined as response (R) = (best response [R1] or second best response [R2])	The method of Thall et al will be used to monitor the probabilities of response.	Up to 56 days
Incidence of acute graft-versus-host disease (GVHD)	The method of Thall et al will be used to monitor the probabilities of grade 3 or 4 GVHD.	Within 28 days of the last dose of cytotoxic T lymphocytes (CTLs)
Incidence of adverse events	Will be continuously monitored.	Up to day 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Each outcome will be evaluated by tabulation and by fitting a Bayesian statistical regression model for binary outcomes as a function of covar. Unadjusted event time distributions will be estimated using the Kaplan-Meier method.	Up to 12 months
Glomerular filtration rate	Each outcome will be evaluated by tabulation and by fitting a Bayesian statistical regression model for binary outcomes as a function of covar. Unadjusted event time distributions will be estimated using the Kaplan-Meier method.	Up to 12 months

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amanda Olson, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: J Clin Oncol. 2023 Oct 20;41(30):4826.

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2015
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: June 19, 2015
• First Submitted That Met QC Criteria: June 23, 2015
• First Posted (Estimated): June 24, 2015

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Slow Virus Diseases; Neuroendocrine Tumors; Carcinoma, Neuroendocrine; Neuroinflammatory Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Encephalitis; Infections; Communicable Diseases; Virus Diseases; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Carcinoma, Merkel Cell; Polyomavirus Infections; Encephalitis, Viral
• Other Study ID Numbers: 2014-0279 (Other Identifier: M D Anderson Cancer Center); NCI-2015-01264 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No