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Leukemia, Myeloid, AcutePhase 1/2PACTNCT02758223

Prophylactic Application of Donor-derived TCM After Allogeneic HSCT

A Phase 1/2 study testing TCM allogeneic humane central memory T cells, cryopreserved in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Wuerzburg University Hospital at 1 site in Germany.

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

PACT is a non-randomized multicentre phase I/II study to evaluate the feasibility and safety of the prophylactic administration of donor derived TCM. Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) who are planned to undergo a HLA -matched (9/10 or 10/10) allogeneic hematopoietic stem cell… Read more about this study

Who is it for?
Ages 50 years and older
What is being tested?
TCM allogeneic humane central memory T cells, cryopreserved
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteGermany
Study dates
Apr 2016to May 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 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient
  • Male or female patients with Hematopoietic Cell Transplant-Co-morbidity Index (HCT-CI) score (Sorror) ≥3 AND/or Age 50 years or older
  • Primary or secondary AML Month 0, Month 1, Month 2, Month 4, Month 5, Month 6 and Month 7, in Complete Remission (CR) (<5% blasts in bone marrow (BM)) irrespective of the cytogenetic or molecular risk profile or MDS up to Refractory anemia with excess of blasts 2 (RAEB-2) (maximal 20% blasts in bone marrow)
  • Planned alloHSCT with Cluster of Differentiation 34+ (CD34+)-purified stem cell grafts after conditioning with fludarabine-melphalan-thio-thepa-ATG (ATG=Antithymocyte globulin)
  • HLA-matched stem cell donor (9-10/10, maximal 1 allel- or antigen mismatch allowed) without aberrant CD45RA (=Cluster of Differentiation) expression
  • Additional patient inclusion criteria: Treatment phase patients at day 30 +/-5 after alloHSCT:
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  • -Stable engraftment of the allogeneic graft (granulocytes > 0.5109/L)
  • Donor
  • Donor must have met requirements of European Union (EU) Tissue and Cells Directive (2004/23/EC) (see below)
  • Healthy donor - having passed medical examination for stem cell donation
  • Donor must fulfill the requirements for allogeneic donor blood testing according to Richtlinie zur Herstellung und Anwendung von hämatopoetischen Stammzellzubereitungen (SC-Richtlinie (RILI) der Bundesärztekammer; 08/2014)
  • Donor informed consent for the additional non-mobilized apheresis
  • Written informed consent of the patient

Who cannot join

  • Patient
  • Disease-specific treatment foreseen in the first 6 months after alloHSCT
  • Patients with AML M3
  • Pregnant or lactating women
  • Severe psychological disturbances
  • Positive serology for Human immunodeficiency virus (HIV), Syphilis, West Nile Virus (WNV)
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  • Participation in another interventional clinical trial during or within 4 weeks before study entry Additional patient exclusion criteria: Treatment phase patients at day 30 +/-5 after alloHSCT:
  • Disease specific treatment foreseen in the first 6 months after alloHSCT
  • Acute GVHD > grade I for which immune suppressive treatment is given
  • Progressive disease for which therapy is needed
  • Use of > 0,5 mg/kg bw prednisone a day
  • Life expectation < 12 weeks
  • End stage irreversible multi-system organ failure
  • Donor
  • Donor pregnant or lactating
  • Donors with aberrant CD45RA isoform expression
  • General exclusion criteria for stem cell donation

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • University Hospital Wuerzburg - Department of Medicine II

    Würzburg

Other trials in Germany

About this study

Official title: Prophylactic Application of Donor-derived Central Memory T Lymphocytes (TCM) After Allogeneic HSCT to Prevent Infectious Complications

PACT is a non-randomized multicentre phase I/II study to evaluate the feasibility and safety of the prophylactic administration of donor derived TCM. Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) who are planned to undergo a HLA -matched (9/10 or 10/10) allogeneic hematopoietic stem cell transplantation and who are either 50+ years old or have a high comorbidity score are included according to criteria as described below. TCM will be applied in escalating doses to a maximum of 30 patients who have received T cell depleted Human leukocyte antigen (HLA)-matched alloHSCT grafts and qualify for TCM transfer.

Read the detailed description

One of the major challenges in the field of allo-SCT is to find a balance between the harmful induction of graft-versus-host disease (GVHD) and the beneficial graft-versus-leukemia (GVL) response, both mediated by donor T cells recognizing antigens expressed on cells of the recipient. Complete removal of T cells from the graft results in abrogation of severe GVHD, but is also frequently associated with removal of the immunity against infectious agents and the anti-tumor efficacy (GVT effect), which is reflected by an increased incidence of infectious complications and (early) disease relapses after T cell depleted allo-SCT. The investigators hypothesize that the prophylactic adoptive transfer of donor-derived central memory T cells is a safe and tolerable method to improve overall survival after HSCT.

TCM are administered in escalating doses at day 30, day 60 and day 90 posttransplant to prevent infectious complications and early relapse or disease progression.

Being tested
TCM allogeneic humane central memory T cells, cryopreserved
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

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

  • TCM allogeneic humane central memory T cells, cryopreservedBiological

    Experimental: TCM allogeneic humane central memory T cells, cryopreserved Solution for injection (intravenous use) up to 65*10^4 TCM /kg body weight patient will receive investigational product 3 times (Day 30, Day 60, Day 90 after alloHSCT)

Study groups in NCT02758223
Study groupRoleWhat they receive
TreatmentExperimentalExperimental: TCM allogeneic humane central memory T cells, cryopreserved Solution for injection (intravenous use) up to 65*10^4 TCM /kg body weight patient will receive investigational product 3 times (Day 30, Day 60, Day 90 after alloHSCT)
Receives: Biological: TCM allogeneic humane central memory T cells, cryopreserved

What is being measured

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

  1. Cumulative incidence of acute GVHD > overall grade II or death

    Toxicity of the infusion will be evaluated by the cumulative incidence of acute GVHD > overall grade II or death during three months after the infusion of the T cell product.

    Measured: during three months after the infusion of the T cell product

Secondary outcomes (10)

  1. Appearance or Expansion of antigen specific T cells measured in specific T cells per mikroliter

    the determination of appearance or expansion of antigen specific T cells (measured in specific T cells per mikroliter) from donor derived TCM during 36 weeks (9 months) after the first infusion of study medication.

    Measured: during 9 months after first infusion

  2. Clinical signs of viral infections - fever in °celsius

    Clinical signs of viral infections - fever in °celsius

    Measured: During 10 months after first application until study end (per patient)

  3. Incidence of relapse

    Measured: During 10 months after first application until study end (per patient)

  4. Incidence of bacterial and fungal infections

    Measured: During 10 months after first application until study end (per patient)

  5. Incidence of GvHD grade II-IV

    Measured: During 10 months after first application until study end (per patient)

  6. Donor chimerism in bone marrow and peripheral blood measured in % of nucleated cells

    Measured: During 10 months after first application until study end (per patient)

  7. Incidence of viremia and clinical manifestations of virus-related organ manifestations (Cytomegalovirus (CMV), Eppstein-Barr virus (EBV), Adenovirus, Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV))

    Measured: During 10 months after first application until study end (per patient)

  8. quantification of CMV specific T cells by multimer staining and ics (copies / ml)

    Efficacy of the transfer of TCM will be evaluated by quantification of CMV specific T cells by multimer staining and ics before transfer of the first TCM dose (Month 0) and at Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8 and Month 9 after first TCM transfer.

    Measured: before transfer of the first TCM dose (Month 0) and at Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8 and Month 9 after first TCM transfer.

  9. quantification of EBV specific T cells by multimer staining and ics (copies / ml)

    Efficacy of the transfer of TCM will be evaluated by quantification of EBV specific T cells by multimer staining and ics before transfer of the first TCM dose (Month 0) and at Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8 and Month 9 after first TCM transfer.

    Measured: before transfer of the first TCM dose (Month 0) and at Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8 and Month 9 after first TCM transfer.

  10. quantification of Adenovirus specific T cells by multimer staining and ics (copies / ml)

    Efficacy of the transfer of TCM will be evaluated by quantification of Adenovirus specific T cells by multimer staining and ics before transfer of the first TCM dose (Month 0) and at Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8 and Month 9 after first TCM transfer.

    Measured: before transfer of the first TCM dose (Month 0) and at Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8 and Month 9 after first TCM transfer.

Timeline

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

  1. First posted2 May 2016 (estimated)
  2. Study startApr 2016
  3. Primary completionMay 2021
  4. Study completionMay 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
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02758223
Sponsor's protocol ID
PACT2014-001
Other IDs
2015-001522-41, 2015
Acronym
PACT
Status last verified
Jul 2022
First submitted
25 Feb 2016
Last updated
13 Jul 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TCM allogeneic humane central memory T cells, cryopreserved in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Wuerzburg University Hospital at 1 site in Germany.

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 13 inclusion and 17 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 13 Jul 2022. 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 Germany. 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?

Cumulative incidence of acute GVHD > overall grade II or death (time frame: during three months after the infusion of the T cell product). 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 NCT02758223.

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 13 Jul 2022.

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