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

Primary Purpose

Acquired Immunodeficiency Syndrome, BK Virus Infection, Human Immunodeficiency Virus

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Allogeneic BK-specific Cytotoxic T-lymphocytes
Laboratory Biomarker Analysis
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acquired Immunodeficiency Syndrome

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (BK-specific cytotoxic T lymphocytes)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
Incidence of adverse events
Will be continuously monitored.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
June 19, 2015
Last Updated
October 2, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02479698
Brief Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 23, 2015 (Actual)
Primary Completion Date
July 31, 2024 (Anticipated)
Study Completion Date
July 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acquired Immunodeficiency Syndrome, BK Virus Infection, Human Immunodeficiency Virus, JC Virus Infection, Malignant Neoplasm, Merkel Cell Carcinoma, Merkel Cell Polyomavirus Infection, Viral Encephalitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (BK-specific cytotoxic T lymphocytes)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Allogeneic BK-specific Cytotoxic T-lymphocytes
Other Intervention Name(s)
Allogeneic BK-CTLs, Allogeneic BK-specific CTLs
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response, defined as response (R) = (best response [R1] or second best response [R2])
Description
The method of Thall et al will be used to monitor the probabilities of response.
Time Frame
Up to 56 days
Title
Incidence of acute graft-versus-host disease (GVHD)
Description
The method of Thall et al will be used to monitor the probabilities of grade 3 or 4 GVHD.
Time Frame
Within 28 days of the last dose of cytotoxic T lymphocytes (CTLs)
Title
Incidence of adverse events
Description
Will be continuously monitored.
Time Frame
Up to day 100
Secondary Outcome Measure Information:
Title
Overall survival
Description
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.
Time Frame
Up to 12 months
Title
Glomerular filtration rate
Description
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.
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda L. Olson, MD
Phone
713-792-8750
Email
ALOlson@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda Olson
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Olson
Phone
713-792-8750
First Name & Middle Initial & Last Name & Degree
Amanda Olson

12. IPD Sharing Statement

Citations:
PubMed Identifier
33929874
Citation
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 Sep 12;:JCO2301860.
Results Reference
derived
PubMed Identifier
30304652
Citation
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.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

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