Preventative/Preemptive Adoptive Transfer of Peptide Stimulated CMV/EBV Specific T-cells in Patients After Allogeneic Stem Cell Transplantation

NCT ID: NCT02227641

Last Updated: 2020-12-14

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

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2017-03-31

Brief Summary

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In patients after allogeneic stem cell transplantation reactivation of latent herpesviruses such as Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) is a frequent and life threatening complication requiring antiviral treatment. The underlying problem is a severe suppression of the donors immune system after transplantation into the patient. Herpesviruses such as CMV and EBV persist after primary infection life long in the host and therefore require constant immunological control. This control is largely provided by the T-cell compartment of the immune system. After allogeneic stem cell transplantation the T-cell compartment requires a long time for its reconstitution since only a small fraction of the donor T-cells are transplanted. During this time Herpesviruses can reoccur due to the lack of effective T-cell control.

This study therefore aims at reconstituting the T-cell compartment with CMV and EBV specific T-cells at an early time point after allogeneic stem cell transplantation. It is mainly a phase I study to demonstrate that these in vitro generated T-cells can be applied safely in this patient population. The study also aims at demonstrating the efficacy of CMV/EBV specific T-cells by monitoring viral reactivation and use of antiviral drugs. The hypothesis is, that CMV/EBV specific T-cell can be applied safely and do not result in graft versus host disease and that they successfully prevent reactivation of CMV and EBV after adoptive transfer in patients after allogeneic stem cell transplantation.

Detailed Description

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Conditions

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Patients Undergoing Allogeneic Stem Cell Transplantation

Keywords

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CMV Cytomegalovirus EBV Epstein Barr Virus virus T cell adoptive transfer transplantation allogeneic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Adoptive transfer of CMV/EBV specific T-cells

Repetitive adoptive T-cell transfer starting at day 30 after allogeneic stem cell transplantation.

Group Type EXPERIMENTAL

CMV/EBV specific T-cell

Intervention Type BIOLOGICAL

Peptide stimulated allogeneic T-cells with dual specificity for CMV and EBV

Control

Observation only.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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CMV/EBV specific T-cell

Peptide stimulated allogeneic T-cells with dual specificity for CMV and EBV

Intervention Type BIOLOGICAL

Other Intervention Names

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T cell

Eligibility Criteria

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Inclusion Criteria

* Indication for allogeneic stem cell transplantation
* HLA identical donor, related or unrelated, 10/10 match
* Stem cell source: G-SCF mobilized peripheral blood stem cells
* Presence of at least one HLA allele: A0101, A0201, B0702, B0801, B3501, C0702
* Positive EBV serology of the donor
* Positive CMV serology of the donor
* Adequate contraception

Exclusion Criteria

* Donor CMV seronegative
* Donor EBV seronegative
* Stem cell source: bone marrow or cord blood
* Alemtuzumab for conditioning
* Sorror Score \>3
* Pregnancy
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role collaborator

University of Regensburg

OTHER

Sponsor Role collaborator

Johannes Gutenberg University Mainz

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

University Hospital Augsburg

OTHER

Sponsor Role collaborator

BayImmuNet Bavarian Immunotherapy Network

UNKNOWN

Sponsor Role collaborator

German Research Foundation

OTHER

Sponsor Role collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Armin H Gerbitz, MD, PhD

Role: STUDY_DIRECTOR

Charite University, Berlin, Germany

Bernd Spriewald, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Erlangen

Anita Kremer, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Erlangen

Katja San Niccolo, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Erlangen

Locations

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Medical Center Augsburg

Augsburg, , Germany

Site Status

Charité University Hospital Berlin

Berlin, , Germany

Site Status

Universitiy Hospital Erlangen

Erlangen, , Germany

Site Status

University of Mainz

Mainz, , Germany

Site Status

University of Munich LMU

Munich, , Germany

Site Status

University of Regensburg

Regensburg, , Germany

Site Status

Countries

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Germany

References

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Gerbitz A, Gary R, Aigner M, Moosmann A, Kremer A, Schmid C, Hirschbuehl K, Wagner E, Hauptrock B, Teschner D, Roesler W, Spriewald B, Tischer J, Moi S, Balzer H, Schaffer S, Bausenwein J, Wagner A, Schmidt F, Brestrich J, Ullrich B, Maas S, Herold S, Strobel J, Zimmermann R, Weisbach V, Hansmann L, Lammoglia-Cobo F, Remberger M, Stelljes M, Ayuk F, Zeiser R, Mackensen A. Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study. Front Immunol. 2023 Oct 30;14:1251593. doi: 10.3389/fimmu.2023.1251593. eCollection 2023.

Reference Type DERIVED
PMID: 37965339 (View on PubMed)

Related Links

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http://www.medizin5.uk-erlangen.de/

Dept. of Medicine 5, Hematology/Oncology, University of Erlangen

Other Identifiers

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2012-004240-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AIT-MULTIVIR-01

Identifier Type: -

Identifier Source: org_study_id