• To evaluate the efficacy of the transfer of multiantigen specific T cells by measuring the appearance or expansion (if antigenic specific donor derived cells are already present in the circulation of the patient at time of infusion) of antigen…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Cumulative incidence of acute GVHD overall grade 3 or higher needing
prolonged systemic immune suppressive treatment in the three months after
infusion of multi antigen-specific T cells.
Secondary outcome
- The appearance or doubling of antigenic specific donor derived T cells in
the circulation during eight weeks after the infusion of multi antigen specific
T cells
- Chimerism in bone marrow and peripheral lymphocytes
- Loads of circulating viruses (CMV, EBV, Adenovirus)
- Disease activity
Background summary
Patients with hematological malignancies can be successfully treated with
allogeneic hematopoietic stem cell transplantation (allo-SCT). 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 associated
with impaired resistance to infections and abrogation of the anti-tumor
efficacy (GVT effect). We hypothesize that the infusion of Streptamer selected
multiantigen specific donor derived T cells early after T cell depleted
allo-SCT is a feasible method to improve anti-viral and anti tumor immunity
without an increased risk of severe GVHD.
Study objective
• To evaluate the efficacy of the transfer of multiantigen specific T cells by
measuring the appearance or expansion (if antigenic specific donor derived
cells are already present in the circulation of the patient at time of
infusion) of antigen specific donor derived T cells during eight weeks after
the infusion of donor derived multi antigen specific T cells.
• To assess the feasibility and safety (toxicity) of the administration of
donor derived multi antigen specific T cells early after T cell depleted
allo-SCT.
• To evaluate whether the appearance or expansion of antigen specific donor
derived T cells coincides with the clearance or prevention of circulating
viruses (EBV, CMV, Adenovirus) or with an improvement in bone marrow chimerism
or with a control in disease burden (malignant cells in blood or bone marrow or
tumor size in case of malignant lymphoma)
Study design
This is a non-randomized phase I/II safety and feasibility study.
Intervention
Patients will receive donor derived multi-antigen specific T cells 6 to 8 weeks
after the transplantation.
Study burden and risks
All study related procedures will be performed during regular control visits
which are scheduled during the first six months after the allogeneic SCT.
Patients will receive one intravenous injection with multi-antigen specific
donor derived T cells to enhance the immune reconstitution. In order to
evaluate the effects of this infusion, one extra bone marrow examination (30
ml) will be performed. In addition, extra blood will be taken during regular
blood examinations (in total 190 ml extra, divided over 5 time points)
A theoretical risk of the infusion of donor derived T cells is the development
of acute Graft Versus Host Disease. Based on our experience maximal 10% of the
patients develops de novo acute GVHD between week 6 and 26 after a T cell
depleted allogeneic SCT. Although the donor derived T cells which are
transferred to the patient in this study are specific for viruses, tumor
associated antigens or haematopoiesis restricted minor antigens, they could
theoretically increase this existing risk on GVHD by intensifying an immune
response towards non-hematopoietic patient tissue.
The potential benefit of the infusion of multi antigen specific T cells is an
increase in donor derived immunity towards viruses and malignant cells in the
patients.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Before allo-SCT:
- Age 18-75 years
- Planned T cell depleted allo-SCT for one of these diagnoses:
* Acute Lymphoblastic Leukemia in CR after prephase and first induction and consolidation therapy and WBC < 30 x 109/l in B-ALL or < 100 x 109/l in T-ALL at initial diagnosis. ALL with t(9;22), t(4;11), complex karyotype or 11q23 abnormalities will be excluded.
* Acute Myeloid Leukemia in CR excluding AML with:
0 Monosomal Karyotype
- Abn3q26
- EVI1 overexpression
* Multiple myeloma at least in stable PR (no treatment foreseen in first 6 months after allo-SCT)
* Non high grade B-NHL (B-CLL, Mantle cell lymphoma, Follicular Lymphoma, MALT, LPL) at least in stable PR (no treatment foreseen in first 6 months after allo-SCT)
* Myeloprolypherative disorder at least in stable PR (no treatment foreseen in first 6 months after allo-SCT), excluding CML blastic phase
* Myelodysplastic/myeloprolypherative neoplasms at least in stable PR (no treatment foreseen in first 6 months after allo-SCT)
* Myelodysplastic syndrome at least in stable PR (no treatment foreseen in first 6 months after allo-SCT)
- HLA type A*0201.
- Written informed consent of the patient
- Availability of a stem cell donor who meets the following inclusion criteria:
* HLA type A*0201
* CMV and/ or EBV seropositivity
* Written informed consent
4-6 weeks after allo-SCT:
- Stable engraftment of the allogeneic graft (platelets >20 *10E9/L, granulocytes > 0.5 *10E9/L)
Exclusion criteria
Before allo-SCT:
- Disease specific treatment foreseen in the first 6 months after SCT
- Life expectation < 6 months.
- End stage irreversible multi-system organ failure (need for mechanical ventilation, hypotension for which admission to ICU, hepatic encephalopathy, coma)
- Pregnant or lactating women or women unwilling or not capable to use effective means of birth control
- Severe psychological disturbances.
4-6 weeks after allo-SCT:
- Histologically proven acute GVHD > grade I for which immune suppressive treatment is given
- Progressive disease for which therapy is needed
- Use of > 20 mg prednisone a day
- Life expectation < 12 weeks.
- End stage irreversible multi-system organ failure (need for mechanical ventilation, hypotension for which admission to ICU, hepatic encephalopathy, coma, start of dialysis after allo-SCT)
6-8 weken na allo-SCT:
- Acute GVHD (preferentially histologically proven) GVHD > grade I for which immune suppressive treatment is given
- Progressive disease for which therapy is needed
- Use of > 20 mg prednisone a day
- Life expectation < 12 weeks.
- End stage irreversible multi-system organ failure (need for mechanical ventilation, hypotension for which admission to ICU, hepatic encephalopathy, coma, start of dialysis after allo-SCT)
- Uncontrolled bacterial or fungal infection.
- Evidence of rejection
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL48393.000.14 |