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

Phase 2

Recruiting

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

• Registration Number: NCT02479698
• Lead Sponsor: M.D. Anderson Cancer Center

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.

Study Timeline

• Study First Submitted: 2015-06-19
• Study First Submitted QC: 2015-06-23
• Study First Posted: 2015-06-24
• Study Start: 2015-07-23
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-04
• Primary Completion: 2025-07-31
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (BK-specific cytotoxic T lymphocytes)	Allogeneic 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.
Treatment (BK-specific cytotoxic T lymphocytes)	Laboratory Biomarker Analysis	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Overall survival	Up to 12 months	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.
Glomerular filtration rate	Up to 12 months	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.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States