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Prophylactic Application of Donor-derived TCM After Allogeneic HSCT (PACT)

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ClinicalTrials.gov Identifier: NCT02758223
Recruitment Status : Recruiting
First Posted : May 2, 2016
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Wuerzburg University Hospital

Brief 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 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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Myelodysplastic Syndromes Biological: TCM allogeneic humane central memory T cells, cryopreserved Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prophylactic Application of Donor-derived Central Memory T Lymphocytes (TCM) After Allogeneic HSCT to Prevent Infectious Complications
Actual Study Start Date : April 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Treatment
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)
Biological: TCM allogeneic humane central memory T cells, cryopreserved
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)




Primary Outcome Measures :
  1. Cumulative incidence of acute GVHD > overall grade II or death [ Time Frame: during three months after the infusion of the T cell product ]
    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.


Secondary Outcome Measures :
  1. Appearance or Expansion of antigen specific T cells measured in specific T cells per mikroliter [ Time Frame: during 9 months after first infusion ]
    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.

  2. Clinical signs of viral infections - fever in °celsius [ Time Frame: During 10 months after first application until study end (per patient) ]
    Clinical signs of viral infections - fever in °celsius

  3. Incidence of relapse [ Time Frame: During 10 months after first application until study end (per patient) ]
  4. Incidence of bacterial and fungal infections [ Time Frame: During 10 months after first application until study end (per patient) ]
  5. Incidence of GvHD grade II-IV [ Time Frame: 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 [ Time Frame: 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)) [ Time Frame: 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) [ Time Frame: 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. ]
    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.

  9. quantification of EBV specific T cells by multimer staining and ics (copies / ml) [ Time Frame: 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. ]
    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.

  10. quantification of Adenovirus specific T cells by multimer staining and ics (copies / ml) [ Time Frame: 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. ]
    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.



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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:

-Stable engraftment of the allogeneic graft (granulocytes > 0.5*109/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

Exclusion Criteria:

  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02758223


Contacts
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Contact: Götz U Grigoleit, PhD 004993120140942 grigoleit_g@ukw.de

Locations
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Germany
University Hospital Wuerzburg - Department of Medicine II Recruiting
Wurzburg, Germany
Contact: Götz Ulrich Grigoleit, PhD    004993120140942    grigoleit_g@ukw.de   
Sponsors and Collaborators
Wuerzburg University Hospital
Investigators
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Principal Investigator: Götz U Grigoleit, PhD University Hospital Wuerzburg- Departement of Medicine II
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Responsible Party: Wuerzburg University Hospital
ClinicalTrials.gov Identifier: NCT02758223    
Other Study ID Numbers: PACT2014-001
2015-001522-41 ( EudraCT Number )
First Posted: May 2, 2016    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases
Neoplasms
Leukemia
Neoplasms by Histologic Type