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

NCT ID: NCT00306332

Last Updated: 2009-08-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

T-cell and B-cell depletion

Intervention Type: PROCEDURE

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Principal Investigators

Nicolaas Schaap, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

476 Hematology, University Medical Centre St Radboud Nijmegen

Nijmegen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 9332335 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10918401 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11516094 (View on PubMed)

Other Identifiers

PSCT10

Identifier Type: -

Identifier Source: org_study_id