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

NCT00306332 | Terminated Phase 3

• 1 other identifier: PSCT10
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia, Myeloid; Leukemia, Lymphocytic; Myelodysplastic Syndrome; Leukemia, Myeloid, Chronic; Lymphoma

Keywords

Allogeneic Stem cell transplantation; T-cell depletion; B-cell depletion; Immunomagnetic selection

Outcome Measures

Primary Outcomes (3)

• relapse

• event-free survival

• survival

Secondary Outcomes (4)

• 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

Interventions

T-cell and B-cell depletion PROCEDURE

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

476 Hematology, University Medical Centre St Radboud Nijmegen

Nijmegen, 6500 HB, Netherlands

Location

Related Publications (3)

• Schaap N, Schattenberg A, Bar 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. doi: 10.1046/j.1365-2141.1997.d01-3499.x.

  PMID: 9332335 BACKGROUND

• 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. doi: 10.1038/sj.bmt.1702451.

  PMID: 10918401 BACKGROUND

• Schaap N, Schattenberg A, Bar 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. doi: 10.1038/sj.leu.2402203.

  PMID: 11516094 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid; Leukemia, Lymphoid; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nicolaas Schaap, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 22, 2006
• First Posted: March 23, 2006
• Study Start: March 1, 2006
• Last Updated: August 18, 2009

Record last verified: 2009-08

Locations

NL (1)