MiHA-loaded PD-L-silenced DC Vaccination After Allogeneic SCT (PSCT19)
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ClinicalTrials.gov Identifier: NCT02528682 |
Recruitment Status :
Completed
First Posted : August 19, 2015
Last Update Posted : April 1, 2021
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Sponsor:
Radboud University Medical Center
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Dutch Cancer Society
Information provided by (Responsible Party):
Radboud University Medical Center
Tracking Information | ||||
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First Submitted Date ICMJE | August 18, 2015 | |||
First Posted Date ICMJE | August 19, 2015 | |||
Last Update Posted Date | April 1, 2021 | |||
Study Start Date ICMJE | January 2016 | |||
Actual Primary Completion Date | March 31, 2021 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | MiHA-loaded PD-L-silenced DC Vaccination After Allogeneic SCT | |||
Official Title ICMJE | Vaccination With PD-L1/L2-silenced Minor Histocompatibility Antigen-loaded Donor DC Vaccines to Boost Graft-versus-tumor Immunity After Allogeneic Stem Cell Transplantation (a Phase I/II Study) | |||
Brief Summary | Allogeneic stem cell transplantation (allo-SCT) is a potent treatment, and sometimes the only curative treatment for aggressive hematological malignancies. The therapeutic efficacy is attributed to the graft-versus-tumor (GVT) response, during which donor-derived CD8+ T cells become activated by recipient minor histocompatibility antigens (MiHA) presented on dendritic cells (DC). Consequently, these alloreactive donor T cells clonally expand, acquire effector functions and kill MiHA-positive malignant cells. However, in a substantial number of patients persistence and recurrence of malignant disease is observed, indicating that insufficient GVT immunity is induced. This is reflected by our observation that not all patients develop a productive CD8+ T cell response towards MiHA mismatched between the recipient and donor. We found that the PD-1/PD-L1 co-inhibitory pathway is involved in dampening MiHA-specific CD8+ T cell expansion and function post-transplantation. Therefore, a promising strategy to induce or boost GVT immune responses is pre-emptive or therapeutic vaccination with ex vivo-generated donor DCs loaded with MiHA that are exclusively expressed by recipient hematopoietic cells and their malignant counterparts. In contrast to pre-emptive donor lymphocyte infusion (DLI) with polyclonal donor T cells, this MiHA-DC vaccination approach has less risk of inducing graft-versus-host disease (GVHD) and the potency to induce more efficient GVT-associated T cell immunity. In addition, the potency of this DC vaccine will be further enhanced by interference with the PD-1/PD-L1 co-inhibitory pathway, using siRNA mediated PD-L1/PD-L2 silencing. | |||
Detailed Description | Not Provided | |||
Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Hematological Malignancies | |||
Intervention ICMJE | Biological: MiHA-loaded PD-L-silenced DC Vaccination
Eligible patients will receive one cycle of donor DC vaccination consisting of maximal 3 immunizations, given at 2 week intervals. PD-L1/L2-silenced, MiHA mRNA-electroporated donor DC will be infused intravenously (2.5x105/kg body weight).
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Study Arms ICMJE | Experimental: Single arm
MiHA-loaded PD-L-silenced DC Vaccination
Intervention: Biological: MiHA-loaded PD-L-silenced DC Vaccination
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
10 | |||
Original Estimated Enrollment ICMJE | Same as current | |||
Actual Study Completion Date ICMJE | March 31, 2021 | |||
Actual Primary Completion Date | March 31, 2021 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Netherlands | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT02528682 | |||
Other Study ID Numbers ICMJE | PSCT19 | |||
Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Radboud University Medical Center | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | Radboud University Medical Center | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Radboud University Medical Center | |||
Verification Date | January 2021 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |