Lymphoma Clinical Trial
Official title:
T-cel and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation by Using Immunomagnetic Negative and Positive Selection Procedures
NCT number | NCT00306332 |
Other study ID # | PSCT10 |
Secondary ID | |
Status | Terminated |
Phase | Phase 3 |
First received | March 22, 2006 |
Last updated | August 17, 2009 |
Start date | March 2006 |
T-cell and B-cell depletion in allogeneic peripheral blood stem cell transplantation by
using immunomagnetic negative and positive selection procedures
Background:
Removal of T-cells from the donor graft (T-cell depletion) offers the possibility for
prevention of GVHD and subsequently less transplant related morbidity and mortality after
allogeneic stem cell transplantation (SCT). There are several techniques to deplete T-cells
from the stem cell grafts e.g. physical, immunological and combined physical / immunological
separation methods. All these techniques result in a stem cell graft with sufficient CD34+
stem cells combined with an adequate depletion of T and B cells. CD34+ selected stem cell
grafts are very pure and do not contain any additional cell populations. In contrast,
CD3+/CD19+ depleted grafts still contain NK-cells, monocytes and dendritic cells that are
part of the innate immune system. Theoretically,the presence of these cells may positively
influence immunological reconstitution and the graft-versus-leukaemia (GVL) effect,
respectively, resulting in improved outcome after SCT
Objectives:
To evaluate the differences in immunological reconstitution, transplant related mortality,
disease-free survival and overall survival after T-cell depleted allogeneic SCT for
haematological malignancies using either immunomagnetic CD34+ selection or immunomagnetic
CD3+/CD19+ depletion using the CliniMACS system in approximately 270 consecutive patients.
Additionally in this study in 20 consecutive patients the kinetics of NK-cel reconstitution
and differences in NK-cell repertoire will be monitored. NK-cell mediated anti-tumor
reactivity will be monitored in patients transplanted with and without NK-cells in the stem
cell graft (CD3+/CD19+ depletion, versus CD34+ selection). Secondary objectives are to
evaluate the clinical relevance of minor histocompatibility-specific cytotoxic T-cell
responses for the GVL effect, the kinetics of NK-cell reconstitution and differences in
NK-cell repertoire using the different T-cell depletion protocols.
Design:
Single center prospective randomised phase III study
Population:
Patients eligible for allogeneic SCT according to the standard criteria of our institution
who will receive an allogeneic T- and B-cell depleted SCT with peripheral stem cells of an
HLA-identical sibling donor or an HLA-identical unrelated voluntary (VUD) donor.
Intervention:
T-cell depletion will be conducted using two different techniques: either immunomagnetic
CD34+ selection or immunomagnetic CD3+/CD19+ depletion.
Endpoints:
Primary endpoints are immunological reconstitution, relapse, disease free survival and
overall survival. Secondary endpoints: NK-cell reconstitution and NK-cell mediated
anti-tumour reactivity. Cytotoxic T-cell responses for the GVL effect.
Estimated efforts and risks for participating patients:
We don't expect any extra patient efforts or risks because T-cell depletion is a standard
procedure in our clinic for many years. There is extensive experience with immunological
T-cell depletion techniques. We hypothesize CD3+/CD19+ depletion will favour stem cell
transplant outcome. Immunological and molecular biological studies will be performed on
blood samples already obtained as part of the standard protocol.
Status | Terminated |
Enrollment | 250 |
Est. completion date | |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria: - Patients with the diagnosis of: - De novo acute myeloid leukaemia in first or second remission. - Secondary acute myeloid leukaemia in first or second remission supervening after myelodysplastic syndrome or cytotoxic / immunosuppressive therapy. - Acute lymphoblastic leukaemia in first or second remission. - Myelodysplastic syndrome. - Chronic myeloid leukaemia, patients who are candidate for SCT. - Malignant lymphoma following relapse or first line therapy resistant. - Aggressive mantle cell lymphoma in first complete remission. - Age 18-65 years. - WHO performance 0-1 (see appendix ). - Availability of an HLA-identical sibling or HLA, A, B, DRB, DQB -identical VUD donor. - Life expectancy > 3 months. - Witnessed written informed consent. Exclusion Criteria: - Patients with severe cardiac dysfunction (NYHA-classification II-IV) - Patients with severe pulmonary dysfunction (vital capacity or diffusion < 70% of predicted value). - Patients with hepatic dysfunction, bilirubin or transaminases > 2.5 x upper normal limit - Patients with renal dysfunction, serum creatinin > 150 umol/liter or clearance < 40 ml/minute. - Patients with a history of moderate ore severe CNS disturbances and psychiatric problems. - Prior treatment with chemotherapy, immunotherapy, radiation therapy or surgery within the last 3 weeks before entering the study. - Patients with active uncontrolled infections. - Patients who are poor medical risks because of non malignant systemic disease. - Patients with severe coagulopathy. - Patients to be known HIV positive. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Netherlands | 476 Hematology, University Medical Centre St Radboud Nijmegen | Nijmegen |
Lead Sponsor | Collaborator |
---|---|
Radboud University |
Netherlands,
Schaap N, Schattenberg A, Bär B, Preijers F, Geurts van Kessel A, van der Maazen R, de Boo T, de Witte T. Outcome of transplantation for standard-risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen. Br J Haematol. 1997 Sep;98(3):750-9. — View Citation
Schaap N, Schattenberg A, Bär B, Preijers F, van de Wiel van Kemenade E, de Witte T. Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions. Leukemia. 2001 Sep;15(9):1339-46. — View Citation
Schattenberg A, Schaap N, Preijers F, van der Maazen R, de Witte T. Outcome of T cell-depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients. Bone Marrow Transplant. 2000 Jul;26(1):17-22. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | relapse | |||
Primary | event-free survival | |||
Primary | survival | |||
Secondary | clinical relevance of mHag-specific CTL responses for the GVL effect | |||
Secondary | Kinetics of NK-cel reconstitution | |||
Secondary | Differences in NK-cell repertoire | |||
Secondary | NK cell mediated anti tumor reactivity |
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