Prophylactic Application of Donor-derived TCM After Allogeneic HSCT - Clinical Trial for Leukemia, Myeloid, Acute | NCT02758223

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

TCM allogeneic humane central memory T cells, cryopreserved

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospital Wuerzburg - Department of Medicine II

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Clinical signs of viral infections - fever in °celsius

Incidence of relapse

Incidence of bacterial and fungal infections

Incidence of GvHD grade II-IV

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

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))

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.

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.

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.

Full Information

NCT ID

NCT02758223

First Posted

February 25, 2016

Last Updated

July 12, 2022

Sponsor

Wuerzburg University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02758223

Brief Title

Prophylactic Application of Donor-derived TCM After Allogeneic HSCT

Acronym

PACT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

April 2016 (Actual)

Primary Completion Date

May 2021 (Actual)

Study Completion Date

May 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wuerzburg University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

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)

Intervention Type

Biological

Intervention Name(s)

TCM allogeneic humane central memory T cells, cryopreserved

Intervention Description

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 Measure Information:

Title

Cumulative incidence of acute GVHD > overall grade II or death

Description

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.

Time Frame

during three months after the infusion of the T cell product

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

during 9 months after first infusion

Title

Clinical signs of viral infections - fever in °celsius

Description

Clinical signs of viral infections - fever in °celsius

Time Frame