Prophylactic Application of Donor-derived TCM After Allogeneic HSCT

NCT ID: NCT02758223

Last Updated: 2022-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2021-05-31

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.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

TCM allogeneic humane central memory T cells, cryopreserved

Intervention Type: BIOLOGICAL

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)

Interventions

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)

Intervention Type: BIOLOGICAL

Eligibility 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

-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)
• 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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wuerzburg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Götz U Grigoleit, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Wuerzburg- Departement of Medicine II

Locations

University Hospital Wuerzburg - Department of Medicine II

Würzburg, , Germany

Countries

Germany

Other Identifiers

2015-001522-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PACT2014-001

Identifier Type: -

Identifier Source: org_study_id