T-cell and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00306332
Recruitment Status : Terminated (Interim analysis has shown that the objectives of this study can not be reached)
First Posted : March 23, 2006
Last Update Posted : August 18, 2009
Information provided by:
Radboud University

March 22, 2006
March 23, 2006
August 18, 2009
March 2006
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  • relapse
  • event-free survival
  • survival
Same as current
Complete list of historical versions of study NCT00306332 on Archive Site
  • 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
Same as current
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T-cell and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation
T-cel and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation by Using Immunomagnetic Negative and Positive Selection Procedures

T-cell and B-cell depletion in allogeneic peripheral blood stem cell transplantation by using immunomagnetic negative and positive selection procedures


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


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.


Single center prospective randomised phase III study


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.


T-cell depletion will be conducted using two different techniques: either immunomagnetic CD34+ selection or immunomagnetic CD3+/CD19+ depletion.


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.

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Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Leukemia, Myeloid
  • Leukemia, Lymphocytic
  • Myelodysplastic Syndrome
  • Leukemia, Myeloid, Chronic
  • Lymphoma
Procedure: T-cell and B-cell depletion
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
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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.
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
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Radboud University
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Principal Investigator: Nicolaas Schaap, MD, PhD Radboud University
Radboud University
August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP