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

NCT ID: NCT02346617

Last Updated: 2020-03-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-01

Study Completion Date

2024-12-01

Brief Summary

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

Detailed Description

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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.

Conditions

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Cytomegalovirus Infections

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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allogeneic HSCT

The present study will investigate in a single-center (Samsung Medical Center), open-label, single arm by direct infusions of donor-derived CMV-spefic IFN-γ positive T-cells for the treatment of refractory CMV infection in allogeneic hematopoietic stem cell transplant (HSCT) recipients.

Group Type EXPERIMENTAL

IFN-γ positive selected T-cells

Intervention Type BIOLOGICAL

No intervention

Interventions

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IFN-γ positive selected T-cells

No intervention

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Miltenyi Biotec B.V. & Co. KG

INDUSTRY

Sponsor Role collaborator

Yae-Jean Kim

OTHER

Sponsor Role lead

Responsible Party

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Yae-Jean Kim

Associate professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Yae-Jean Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Locations

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Samsung Medical Center

Seoul, Gangnam-Gu, South Korea

Site Status

Countries

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South Korea

References

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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.

Reference Type BACKGROUND
PMID: 23198963 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20625005 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21148519 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19911966 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22318829 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19747629 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19299333 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 22566808 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20719569 (View on PubMed)

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. doi: 10.1097/01.tp.0000229390.01369.4a.

Reference Type BACKGROUND
PMID: 16926601 (View on PubMed)

Other Identifiers

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SMC 2010-08-129-008

Identifier Type: -

Identifier Source: org_study_id

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