T-cell and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia, Myeloid Leukemia, Lymphocytic Myelodysplastic Syndrome Leukemia, Myeloid, Chronic Lymphoma |
Procedure: T-cell and B-cell depletion |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | T-cel and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation by Using Immunomagnetic Negative and Positive Selection Procedures |
- relapse
- event-free survival
- survival
- clinical relevance of mHag-specific CTL responses for the GVL effect
- Kinetics of NK-cel reconstitution
- Differences in NK-cell repertoire
- NK cell mediated anti tumor reactivity
| Estimated Enrollment: | 250 |
| Study Start Date: | March 2006 |
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Netherlands | |
| 476 Hematology, University Medical Centre St Radboud Nijmegen | |
| Nijmegen, Netherlands, 6500 HB | |
| Principal Investigator: | Nicolaas Schaap, MD, PhD | Radboud University |
More Information
Publications:
| ClinicalTrials.gov Identifier: | NCT00306332 History of Changes |
| Other Study ID Numbers: | PSCT10 |
| Study First Received: | March 22, 2006 |
| Last Updated: | August 17, 2009 |
| Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Keywords provided by Radboud University:
|
Allogeneic Stem cell transplantation T-cell depletion B-cell depletion Immunomagnetic selection |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Lymphoma Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms |
Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Precancerous Conditions |
ClinicalTrials.gov processed this record on May 19, 2013