Prophylactic Application of Donor-derived TCM After Allogeneic HSCT

NCT02758223 | Completed Phase 1 DMC

• 2 other identifiers: PACT2014-0012015-001522-41
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (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.

  during three months after the infusion of the T cell product

Secondary Outcomes (10)

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

  during 9 months after first infusion

• Clinical signs of viral infections - fever in °celsius

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

• Incidence of relapse

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

• Incidence of bacterial and fungal infections

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

• Incidence of GvHD grade II-IV

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

Study Arms (1)

Treatment

EXPERIMENTAL

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

Interventions

TCM allogeneic humane central memory T cells, cryopreserved 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)

Treatment

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wuerzburg University Hospital: lead

Study Sites (1)

University Hospital Wuerzburg - Department of Medicine II

Würzburg, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Cryopreservation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Tissue Preservation; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Preservation, Biological; Therapeutics; Investigative Techniques

Study Officials

• Götz U Grigoleit, PhD

  University Hospital Wuerzburg- Departement of Medicine II

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2016
• First Posted: May 2, 2016
• Study Start: April 1, 2016
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: July 13, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)