In this study, haploidentical relatives of a patient with recurrent or metastatic HPV 16-associated malignancy will be vaccinated with a therapeutic human papillomavirus (HPV) vaccine series to generate HPV-specific leukocytes. The cancer patient with recurrent or metastatic HPV16+ cancer will then be randomized to one of two arms: 1) non-myeloablative allogeneic bone marrow transplant or 2) cluster of differentiation 8 (CD8)-depleted donor lymphocyte infusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Patients will receive CD8+ T cell-depleted peripheral blood cells at one of three dose levels following cyclophosphamide: 1) 10\^6 CD4+ cells/kg; 2) 5 x 10\^6 CD4+ cells/kg; or 3) 10\^7 CD4+ cells/kg of recipient ideal body weight.
Standard dosing for bone marrow graft (target dose of 4 x 10\^8 nucleated cells/kg) and if progression at Day 90, will receive dose level 1 for the CD8-depleted DLI (106 CD4+ cell/kg).
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
RECRUITINGSafety as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Determine the safety of the two interventions in patients with recurrent or metastatic HPV16-associated cancer. Safety will be monitored for every patient and we will document and grade every adverse event using the NCI CTCAE version 5.0.
Time frame: 12 months
Maximum Tolerated Dose (MTD) of Allogeneic CD4+ T cell Infusion
Determine the maximum tolerated dose (in CD4+ cells/kg) of allogeneic CD4+ T cells infused after cyclophosphamide in patients with recurrent or metastatic HPV16-associated cancer. We will use three dose levels of allogeneic CD4+ T cells: 1) 10\^6 CD4+ cells/kg; 2) 5 x 10\^6 CD4+ cells/kg; 3) 10\^7 CD4+ cells/kg of recipient ideal body weight. We will implement a Bayesian optimal interval design to find the MTD with an observation period of 42 days for treatment-related toxicities.
Time frame: 12 months
Number of toxicities as assessed by the NCI CTCAE version 5.0
Count the toxicities of allogeneic BMT and HPV-specific CD4+ T cells in patients with recurrent or metastatic HPV16-associated cancer. Toxicities of treatment will be formally assessed and scored using the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: 12 months
Progression-free survival (PFS) of allogeneic CD4+ T cell Infusion and allogeneic BMT
PFS is defined as the date from transplantation to the date of relapse/progression, death from any cause or last follow-up, whichever comes first. Kaplan-Meier curve will be generated and PFS will be estimated along with 95% confidence intervals.
Time frame: 12 months
Overall survival (OS) of allogeneic CD4+ T cell Infusion and allogeneic BMT
OS is defined as the date from infusion or transplantation to the date of death from any cause or last follow-up. A Kaplan-Meier curve will be generated along with 95% confidence intervals.
Time frame: 12 months
Overall Response of allogeneic CD4+ T cell Infusion and allogeneic BMT
Response will be defined as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and will be evaluated at 2, 6 and 12 months after transplantation or infusion.
Time frame: Up to 12 months
Incidence of acute graft versus host disease (GVHD)
Each patient will be monitored for acute GVHD and we will grade acute GVHD using the consensus conference clinical grading of acute GVHD.
Time frame: 12 months
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