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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02479698

Collaborator

National Cancer Institute (NCI) (NIH)

100

Enrollment

Location

Arm

84.3

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acquired Immunodeficiency Syndrome BK Virus Infection Human Immunodeficiency Virus JC Virus Infection Malignant Neoplasm Merkel Cell Carcinoma Merkel Cell Polyomavirus Infection Viral Encephalitis	Biological: Allogeneic BK-specific Cytotoxic T-lymphocytes Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 23, 2015

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

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.	Biological: Allogeneic BK-specific Cytotoxic T-lymphocytes Given IV Other Names: Allogeneic BK-CTLs Allogeneic BK-specific CTLs Other: Laboratory Biomarker Analysis Correlative studies

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.

Biological: Allogeneic BK-specific Cytotoxic T-lymphocytes

Given IV

Other Names:

Allogeneic BK-CTLs

Allogeneic BK-specific CTLs

Other: Laboratory Biomarker Analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

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 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.
Incidence of adverse events [Up to day 100]
Will be continuously monitored.

Secondary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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