Clinical trial NCT02346617: Adoptive Transfer of pp65-specific T Cells for the Treatment of Refractory Cytomegalovirus (CMV) Infection
Official title: Adoptive Transfer of pp65-specific T Cells for the Treatment of Refractory Cytomegalovirus (CMV) Infection in Allogeneic Hematopoietic Cell Transplant Recipients
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Cytomegalovirus Infections
Keywords: CMV
T cell therapy
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Miltenyi Biotec B.V. & Co. KG
First posted: 2015-01-27
Enrollment: 0
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy for treatment of persistent CMV infection in hematopoietic cell transplant (HCT) recipients.

Detailed description: HCT recipients who are receiving immunosuppressive agents to control graft versus host diseases (GVHD) are at high risk for serious CMV infection due to CMV reactivation or reinfection during their post-transplant period.

Antiviral agents used to treat CMV infection have well-known side effects such as bone marrow suppression causing cytopenia and renal toxicities. Therefore, patients in a serious condition would have a higher probability of antiviral treatment-related toxicities and also increased possibility for prolonged antiviral treatment, thus development of antiviral resistance and risk of treatment failure.

Allogeneic HCT recipients are typically lack of these CMV-specific T cells during the post-transplant period and their immune function can be further repressed especially when they are on additional immunosuppressive agents to prevent GVHD. Therefore, these patients may benefit from CMV-specific T cell adoptive transfer.

Eligibility criteria: Inclusion Criteria:

* Less than 66 years old Allogeneic HCT recipients who received stem cells from related CMV positive serology donors
* AND recipients have persistent CMV infection more than 2 weeks on antiviral treatment

Exclusion Criteria:

* HCT recipients with severe graft versus host disease, grade 3 or more
* OR organ dysfunction (brain, heart, lung, liver, and kidney): altered mentality, extracorporeal membrane oxygenation, mechanical ventilator, increased liver enzymes 5 times above upper normal values, bilirubin level \>3 mg/dL, CrCl \< 30 mL/min

Primary outcomes:
measure: Level of enriched IFN-Υ+ T-cells upon pp65 stimulation
timeFrame: 2 weeks
Secondary outcomes:
measure: Treatment efficacy of CMV infection, defined as reduction of CMV viremia, ex vivo enrichment of CMV antigen (pp65) -specific T cells in peripheral blood.
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-Gu
Study officials:
affiliation: Samsung Medical Center
name: Yae-Jean Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim YJ, Boeckh M, Cook L, Stempel H, Jerome KR, Boucek R Jr, Burroughs L, Englund JA. Cytomegalovirus infection and ganciclovir resistance caused by UL97 mutations in pediatric transplant recipients. Transpl Infect Dis. 2012 Dec;14(6):611-7. doi: 10.1111/j.1399-3062.2012.00760.x.
citation: Feuchtinger T, Opherk K, Bethge WA, Topp MS, Schuster FR, Weissinger EM, Mohty M, Or R, Maschan M, Schumm M, Hamprecht K, Handgretinger R, Lang P, Einsele H. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010 Nov 18;116(20):4360-7. doi: 10.1182/blood-2010-01-262089. Epub 2010 Jul 12.
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citation: Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ; Center for International Blood and Marrow Research; National Marrow Donor program; European Blood and MarrowTransplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow Transplant Group; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America; Association of Medical Microbiology and Infectious Disease Canada; Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009 Oct;15(10):1143-238. doi: 10.1016/j.bbmt.2009.06.019. No abstract available.
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