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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001522-41 | EudraCT Number |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | during 9 months after first infusion |
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Inclusion Criteria:
Patient
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
Exclusion Criteria:
Donor
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| Name | Affiliation | Role |
|---|---|---|
| Götz U Grigoleit, PhD | University Hospital Wuerzburg- Departement of Medicine II | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Wuerzburg - Department of Medicine II | Würzburg | Germany |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D015925 | Cryopreservation |
| ID | Term |
|---|---|
| D014021 | Tissue Preservation |
| D016591 | Histocytological Preparation Techniques |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
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|
| Clinical signs of viral infections - fever in °celsius | 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) |
| Donor chimerism in bone marrow and peripheral blood measured in % of nucleated cells | During 10 months after first application until study end (per patient) |
| 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)) | During 10 months after first application until study end (per patient) |
| 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. | 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. | 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. | 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. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D006652 | Histological Techniques |
| D011309 | Preservation, Biological |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |