Clinical Trial Results:
PSCT16 Study: Vaccination with minor histocompatibility antigenloaded donor DC vaccines to boost graft-versus-tumor immunity after allogeneic stem cell transplantation
PSCT19 Study: 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)
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Summary
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EudraCT number |
2012-002879-34 |
Trial protocol |
NL |
Global end of trial date |
06 Oct 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Dec 2021
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First version publication date |
13 Dec 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PSCT16 & PSCT19
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Radboud University Medical Center Nijmegen
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Sponsor organisation address |
Geert Grooteplein Zuid 8, Nijmegen, Netherlands, 6500 HB
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Public contact |
Trialbureau Hematologie-Oncologie, Radboud University Nijmegen Medical Centre, 31 243614794, studies.hemat@radboudumc.nl
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Scientific contact |
Trialbureau Hematologie-Oncologie, Radboud University Nijmegen Medical Centre, 31 243614794, studies.hemat@radboudumc.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Oct 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Oct 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Primary Objective PSCT16:
-to evaluate the safety and toxicity of pre-emptive administration of donor DCs electroporated with
mRNA encoding hematopoietic-restricted MiHA.
-to evaluate the capability and strength (i.e. % MiHA-specific T cells within total CD8+ T population) of
MiHA mRNA-loaded donor DC to induce in vivo expansion of CD8+ memory T cells against
hematopoietic-restricted MiHA.
-to evaluate the immune response to KLH
Primary Objective PSCT19:
The study is designed as a phase I/II study in 10 patients who had undergone HLA-matched
allogeneic SCT:
-to evaluate the toxicity of pre-emptive administration of PD-L1/L2-silenced donor DCs electroporated
with mRNA encoding hematopoietic-restricted MiHA.
-to evaluate the capability and strength (i.e. % MiHA-specific T cells within total CD8+ T population) of
MiHA mRNA-loaded donor DC to induce in vivo expansion of CD8+ memory T cells against
hematopoietic-restricted MiHA.
-to evaluate the immune response to KLH
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Protection of trial subjects |
The responsible investigator will ensure that this study is conducted in agreement with either the
Declaration of Helsinki (Tokyo, Venice, Hong Kong, Somerset West and Edinburgh amendments), or the laws and regulations of the country whichever provides the greatest protection of the patient.
The design of this study follows current views of the European Medicine Agency (EMA) for Advanced
Medicinal Therapy Products (AMTP) in general and for Cellular Advanced Therapeutics (CAT) in
particular.
The protocol has been written, and the study will be conducted according to the guidelines for Good
Clinical Practice and Good Manufacturing Practice issued by the European Union.
The protocol has been approved by the Central Committee on Research Involving Human Subjects
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Background therapy |
No background therapy was given | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
03 Jun 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 16
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Worldwide total number of subjects |
16
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EEA total number of subjects |
16
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
13
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Prior to allogeneic stem cell transplantation HLA-A2+ and HLA-B7+ recipient donor pairs were asked permission for genotyping for MiHA mismatches for HA-1, LRH-1 and ARHGDIB. Patients with MiHA mismatches in the graft-versus-tumor direction, who met the inclusion criteria were asked informed consent for this dendritic cell vaccination study | |||||||||
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Pre-assignment
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Screening details |
For the pilot study (PSCT16), 17 patients were screened, of whom 4 included. One patient was withdrawn because he did not fulfill the criteria. For the PSCT19 study, 48 patients were screened, of whom 12 included. The screening criteria can be found in the protocols. | |||||||||
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Period 1
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Period 1 title |
Overall trial
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Pilot PSCT16 study | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
MiHA mRNA-electroporated mature DCs
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
20x10^6 MiHA mRNA-electrocoporated mature DCs were infused on day 0, 14 and 28
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Arm title
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PSCT19 study | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
monocyte-derived, PD-L1/L2-silenced donor DCs electroporated with mRNA encoding hematopoietic-restricted MiH
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Monocyte-derived, PD-L1/L2-silenced donor DCs electroporated with mRNA encoding hematopoietic-restricted MiH, 2,5x10^5/kg, intravenous on day 0, 14, and 28
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Period 2
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Period 2 title |
During treatment
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Is this the baseline period? |
No | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Pilot PSCT16 study | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
MiHA mRNA-electroporated mature DCs
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
20x10^6 MiHA mRNA-electrocoporated mature DCs were infused on day 0, 14 and 28
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Arm title
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PSCT19 study | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
monocyte-derived, PD-L1/L2-silenced donor DCs electroporated with mRNA encoding hematopoietic-restricted MiH
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Monocyte-derived, PD-L1/L2-silenced donor DCs electroporated with mRNA encoding hematopoietic-restricted MiH, 2,5x10^5/kg, intravenous on day 0, 14, and 28
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| Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 16 subjects were included in the study, 3 patients did not start the study *In the PSCT16 study one patient did not meet inclusion criteria so this patient was not treated *In the PSCT19 study one patient dit not start treatment because the donor did nog give consent for monocyte aferesis, *In the PSCT19 study one patient did not have the right HLA type |
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Period 3
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Period 3 title |
After the end of treatment (Follow-up)
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Is this the baseline period? |
No | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Pilot PSCT16 study | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
MiHA mRNA-electroporated mature DCs
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
20x10^6 MiHA mRNA-electrocoporated mature DCs were infused on day 0, 14 and 28
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Arm title
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PSCT19 study | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
monocyte-derived, PD-L1/L2-silenced donor DCs electroporated with mRNA encoding hematopoietic-restricted MiH
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Monocyte-derived, PD-L1/L2-silenced donor DCs electroporated with mRNA encoding hematopoietic-restricted MiH, 2,5x10^5/kg, intravenous on day 0, 14, and 28
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pilot PSCT16 study
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Reporting group description |
- | ||
Reporting group title |
PSCT19 study
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Reporting group description |
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Reporting group title |
Pilot PSCT16 study
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Reporting group description |
- | ||
Reporting group title |
PSCT19 study
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Reporting group description |
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Reporting group title |
Pilot PSCT16 study
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Reporting group description |
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Reporting group title |
PSCT19 study
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Reporting group description |
- | ||
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End point title |
Toxicity - Adverse events [1] | |||||||||||||||||||||||||||||||||||||||
End point description |
Adverse events > grade 2 according to CTCAE in PSCT16 trial and adverse events > grade 1 to CTCAE in
PSCT 19 trial
Serious adverse events
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End point type |
Primary
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End point timeframe |
Patiënts were screened for adverse events during study visits.
The study visits were: prestudy, day 0, day 7, day 14, day 21, day 28, day 42, day 63 and day 84.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a phase 1 trial, so adverse events are described and not compared between the two groups. |
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| Notes [2] - Adverse events > CTCEA grade 2 (according to study protocol) [3] - Adverse events > CTCAE grade 1 |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||
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End point title |
GVHD [4] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Patiënts were screened for adverse events during study visits.
The study visits were: prestudy, day 0, day 7, day 14, day 21, day 28, day 42, day 63 and day 84.
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis is not applicable for this endpoint. Graft-versus-host disease dit not occur in any of the reporting groups. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Immunological response of MiHA CD8+ T cells [5] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The amount of MiHA specific CD8+ cells was counted prestudy and on day 0, 7, 14, 21, 28, 35, 63 and 84
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This analysis is still ongoing |
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| Notes [6] - This analysis is still ongoing [7] - This analysis is still ongoing |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All adverse events reported spontaneously by the subject or observed by the investigator or his staff
occuring until 84 days after the first DC vaccination will be recorded in the eCRF.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI-CTCAE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
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Reporting groups
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Reporting group title |
Pilot PSCT16 study
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Reporting group description |
All patients included in the study who received at least one dose of treatment. AE's of CTCAE grade 1 and 2 are not considered AE's in this protocol. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PSCT19 study
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Reporting group description |
AEs of CTCAE grade 1 are not considered adverse events in this study | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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31 Jan 2018 |
Amendement concering PSCT19 trial
-Hodgkin lymphoma has been added to inclusion criteria
-Patiënts can be included after tapering of immune suppression instead of after tapering of ciclosporin A
-Adverse events of grade 2 or higher will be described in the CRF
-Donors will have a 12 liter apheresis instead of a 9 liter apheresis
-Follow up will be performed on day 35 instead of day 42 |
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04 Jul 2019 |
Patients with myeloprolifertive neoplasms can be included in the study |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
