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

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ClinicalTrials.gov Identifier: NCT02479698
Recruitment Status : Recruiting
First Posted : June 24, 2015
Last Update Posted : July 19, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE June 19, 2015
First Posted Date  ICMJE June 24, 2015
Last Update Posted Date July 19, 2021
Actual Study Start Date  ICMJE July 23, 2015
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2019)
  • Response, defined as response (R) = (best response [R1] or second best response [R2]) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Up to day 100 ]
    Will be continuously monitored.
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2015)
  • Success of Anti-Viral Activity [ Time Frame: 28 days ]
    Success defined as viral response at 28 days. Complete response: Complete resolution of symptoms and gross hematuria. A decrease from grade 2 (macroscopic hematuria), grade 3 (urinary blood clots) or grade 4 (red cell transfusion requirement/renal impairment) to grade 0 (no hematuria or grade 1 (microscopic hematuria). Partial response: Decrease in grade of HC from grade 3 (urinary blood clots) or 4 (red cell transfusion requirement or renal impairment) to grade 2 (macroscopic hematuria). Stable disease: Changes insufficient to qualify as partial response or progression. Progression: Increase in symptoms from baseline or worsening hematuria, increase in grade of HC (2-4).
  • Secondary Graft Failure [ Time Frame: 28 days ]
    Secondary graft failure defined as initial neutrophil engraftment followed by subsequent decline in the ANC to < 500/mm3 for three consecutive measurements on different days, unresponsive to growth factor therapy that persists for at least 14 days in the absence of a known cause such as relapse. Secondary graft failure assessed at 28 days after the last infusion of third-party CTLs.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2019)
  • Overall survival [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cytotoxic T Lymphocytes in Treating Patients With Malignancies With BK and/or JC Virus
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acquired Immunodeficiency Syndrome
  • BK Virus Infection
  • Human Immunodeficiency Virus
  • JC Virus Infection
  • Malignant Neoplasm
  • Merkel Cell Carcinoma
  • Merkel Cell Polyomavirus Infection
  • Viral Encephalitis
Intervention  ICMJE
  • Biological: Allogeneic BK-specific Cytotoxic T-lymphocytes
    Given IV
    Other Names:
    • Allogeneic BK-CTLs
    • Allogeneic BK-specific CTLs
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Arms  ICMJE 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.
Interventions:
  • Biological: Allogeneic BK-specific Cytotoxic T-lymphocytes
  • Other: Laboratory Biomarker Analysis
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2018)
100
Original Estimated Enrollment  ICMJE
 (submitted: June 23, 2015)
30
Estimated Study Completion Date  ICMJE July 31, 2021
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amanda L. Olson, MD 713-792-8750 ALOlson@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02479698
Other Study ID Numbers  ICMJE 2014-0279
NCI-2015-01264 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0279 ( Other Identifier: M D Anderson Cancer Center )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Amanda Olson M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP