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

This study has been terminated.
(Interim analysis has shown that the objectives of this study can not be reached)
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00306332
First received: March 22, 2006
Last updated: August 17, 2009
Last verified: August 2009
  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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • relapse
  • event-free survival
  • survival

Secondary Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00306332

Locations
Netherlands
476 Hematology, University Medical Centre St Radboud Nijmegen
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
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, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions

ClinicalTrials.gov processed this record on November 20, 2014