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Hematological MalignanciesPhase 1/2PSCT19NCT02528682

MiHA-loaded PD-L-silenced DC Vaccination After Allogeneic SCT

A Phase 1/2 study testing MiHA-loaded PD-L-silenced DC Vaccination in people with Hematological Malignancies, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hematological Malignancies
What is being tested?
MiHA-loaded PD-L-silenced DC Vaccination
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteNetherlands
Study dates
Jan 2016to 31 Mar 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with AML, myelodysplasia (MDS), ALL, CML (accelerated or blast phase), CLL, MM, malignant NHL or HL, who underwent HLA-matched allo-SCT
  • Patients positive for HLA-A2 and/or HLA-B7
  • Patients positive for HA-1, LRH-1 and/or ARHGDIB transplanted with corresponding MiHA-negative donor
  • Patients ≥18 years of age
  • WHO performance 0-2
  • Witnessed written informed consent

Who cannot join

  • Life expectancy < 3 months
  • Severe neurological or psychiatric disease
  • Progressive disease needing cytoreductive therapy
  • HIV positivity
  • Patients with acute GVHD grade 3 or 4
  • Patients with severe chronic GVHD
Show all 12Show fewer
  • Patients with active infections (viral, bacterial or fungal) that require specific therapy. Acute anti-infectious therapy must have been completed within 14 days prior to study treatment
  • Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease)
  • Severe pulmonary dysfunction
  • Severe renal dysfunction (serum creatinine > 3 times normal level)
  • Severe hepatic dysfunction (serum bilirubin or transaminases > 3 times normal level)
  • Patients with known allergy to shell fish

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Trialoffice Haematology-Oncology

    Nijmegen, Gelderland, 6500 HB

Other trials in Netherlands

About this study

Official title: 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)

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.

Being tested
MiHA-loaded PD-L-silenced DC Vaccination
Keywords
dendritic cells, PD-L1/L2 silencing, vaccination, stem cell transplantation, minor histocompatibility antigens
Medical subject headings
Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MiHA-loaded PD-L-silenced DC VaccinationBiological

    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).

Study groups in NCT02528682
Study groupRoleWhat they receive
Single armExperimentalMiHA-loaded PD-L-silenced DC Vaccination
Receives: Biological: MiHA-loaded PD-L-silenced DC Vaccination

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluation of toxicity

    Toxicity will be measured using the NCI CTCAE criteria (http://ctep.cancer.gov/reporting/ctc.html). Possible toxicities include constitutional symptoms such as fever, chills, myalgias, malaise and allergic reactions.

    Measured: From day 0 until day 84

  2. Development of GVHD

    DC vaccination may result in GVHD, which will be scored and treated if indicated according to standard guidelines.

    Measured: From day 0 until day 84

  3. The generation and magnitude of an immunological response

    When after DC vaccination >1.0% of all CD8+ lymphocytes at any time point are specific CD8+ T cells to the used MiHA vaccine target, a complete response will be considered to be present. When the percentage is between 0.02% and 1%, but has been doubled during two weeks, a partial immune response will be considered to be present.

    Measured: From day 0 until day 84

Secondary outcomes (2)

  1. Changes in chimerism

    When chimerism changes towards donor or disease load decreases according to objective standard clinical criteria after vaccination, this will be considered as a clinical response.

    Chimerism in PBMC will be measured by SNP Q-PCR analysis according to standard practice in the molecular diagnostic unit of Department of Laboratory Medicine. When chimerism changes towards complete donor, this will be considered as a clinical response.

    Measured: day 0, day 14, day 28, day 64, day 84

  2. Disappearance of residual disease

    In the case of presence of detectable residual or persistent disease before DC vaccination, clinical effects will be investigated by monitoring residual disease by quantitative real-time bcr-abl PCR (CML, Ph+ ALL), WT1-specific PCR (AML, MDS), M-protein (MM), immunophenotyping (CLL, AML, ALL, MDS) and radiological examination (NHL) after vaccination. When disease load decreases according to objective standard clinical criteria after vaccination, this will be considered as a clinical response.

    Measured: day 0, day 14, day 28, day 64, day 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2015 (estimated)
  2. Study startJan 2016
  3. Primary completion31 Mar 2021
  4. Study completion31 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02528682
Sponsor's protocol ID
PSCT19
Acronym
PSCT19
Status last verified
Jan 2021
First submitted
18 Aug 2015
Last updated
1 Apr 2021
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MiHA-loaded PD-L-silenced DC Vaccination in people with Hematological Malignancies, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluation of toxicity (time frame: From day 0 until day 84). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02528682.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.

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