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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

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

Full Information

NCT ID

NCT02479698

First Posted

June 19, 2015

Last Updated

October 2, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

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

Data Monitoring Committee

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

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

Time Frame

Up to 12 months

Title

Glomerular filtration rate

Description

Time Frame

Up to 12 months

10. Eligibility

Sex

All

Accepts Healthy Volunteers

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

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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