Adoptive Transfer of pp65-specific T Cells for the Treatment of Refractory Cytomegalovirus (CMV) Infection

Cytomegalovirus Infections Clinical Trial

Official title:

Adoptive Transfer of pp65-specific T Cells for the Treatment of Refractory Cytomegalovirus (CMV) Infection in Allogeneic Hematopoietic Cell Transplant Recipients

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02346617
• Other study ID #: SMC 2010-08-129-008
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: January 1, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: March 2020
• Source: Samsung Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• Infection

Intervention

Biological:
• IFN-? positive selected T-cells
No intervention

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul	Gangnam-Gu

Sponsors (2)

Lead Sponsor	Collaborator
Yae-Jean Kim	Miltenyi Biotec B.V. & Co. KG

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (10)

Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood. 2009 Jun 4;113(23):5711-9. doi: 10.1182/blood-2008-10-143560. Epub 2009 Mar 18. Review. — View 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. — View Citation

Hadaya K, Avila Y, Valloton L, de Rham C, Bandelier C, Ferrari-Lacraz S, Pascual M, Pantaleo G, Martin PY, Buhler L, Villard J. Natural killer cell receptor--repertoire and functions after induction therapy by polyclonal rabbit anti-thymocyte globulin in unsensitized kidney transplant recipients. Clin Immunol. 2010 Nov;137(2):250-60. doi: 10.1016/j.clim.2010.07.004. Epub 2010 Aug 17. — View 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. — View Citation

Peggs KS, Thomson K, Samuel E, Dyer G, Armoogum J, Chakraverty R, Pang K, Mackinnon S, Lowdell MW. Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin Infect Dis. 2011 Jan 1;52(1):49-57. doi: 10.1093/cid/ciq042. — View Citation

Peggs KS, Verfuerth S, Pizzey A, Chow SL, Thomson K, Mackinnon S. Cytomegalovirus-specific T cell immunotherapy promotes restoration of durable functional antiviral immunity following allogeneic stem cell transplantation. Clin Infect Dis. 2009 Dec 15;49(12):1851-60. doi: 10.1086/648422. — View 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. Erratum in: Biol Blood Marrow Transplant. 2010 Feb;16(2):294. Boeckh, Michael A [corrected to Boeckh, Michael J]. — View Citation

Vacher-Coponat H, Brunet C, Moal V, Loundou A, Bonnet E, Lyonnet L, Ravet S, Sampol-Manos E, Sampol J, Berland Y, George FD, Paul P. Tacrolimus/mycophenolate mofetil improved natural killer lymphocyte reconstitution one year after kidney transplant by reference to cyclosporine/azathioprine. Transplantation. 2006 Aug 27;82(4):558-66. — View Citation

Vivier E, Ugolini S. Natural killer cells: from basic research to treatments. Front Immunol. 2011 Jun 3;2:18. doi: 10.3389/fimmu.2011.00018. eCollection 2011. — View Citation

Yi ES, Kim YJ. Cytomegalovirus infection according to cell source after hematopoietic cell transplantation in pediatric patients. Yonsei Med J. 2012 Mar;53(2):393-400. doi: 10.3349/ymj.2012.53.2.393. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level of enriched IFN-?+ T-cells upon pp65 stimulation		2 weeks
Secondary	Treatment efficacy of CMV infection, defined as reduction of CMV viremia, ex vivo enrichment of CMV antigen (pp65) -specific T cells in peripheral blood.	Treatment efficacy defined as reduction of CMV viremia, ex vivo enrichment of CMV antigen (pp65) -specific T cells in peripheral blood.	2 weeks