Nonmyeloablative Stem Cell Transplantation With CD8-depleted or Unmanipulated Peripheral Blood Stem Cells (PBSC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yves Beguin, University Hospital of Liege
ClinicalTrials.gov Identifier:
NCT00693927
First received: May 29, 2008
Last updated: September 1, 2011
Last verified: September 2011
  Purpose

Prospective randomized study of allogeneic minitransplantation from HLA-identical family or unrelated donors comparing unmanipulated or CD8-depleted PBSC. The conditioning regimen will be 2 Gy TBI alone (related donor with low-risk of transplant rejection) or 2 Gy TBI and 3 x 30 mg/m2 fludarabine (unrelated donor or high risk of transplant rejection). Patients will receive a short but intensive immunosuppressive treatment (cyclosporine and mycophenolate mofetil) to ensure both graft-versus-host and host-versus-graft tolerance. The rationale for using PBSC instead of marrow transplant is to avoid general anesthesia of the donor and to minimize the risk of rejection. The rationale for CD8+ depletion is to diminish the risk of GVHD after PBSC transplantation or DLI.


Condition Intervention Phase
Hematologic Malignancies
Procedure: Unmanipulated PBSC after nonmyeloablative conditioning
Procedure: CD8-depleted PBSC after nonmyeloablative conditioning
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nonmyeloablative Stem Cell Transplantation With CD8-depleted or Unmanipulated Peripheral Blood Stem Cells: A Prospective Randomized Phase II Trial

Resource links provided by NLM:


Further study details as provided by University Hospital of Liege:

Primary Outcome Measures:
  • Incidence of acute GVHD in CD8-depleted versus unmanipulated groups [ Time Frame: 180 days ] [ Designated as safety issue: No ]
  • Incidence of chronic GVHD (overall and extensive) in CD8-depleted versus unmanipulated groups. [ Time Frame: 1-year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of graft rejection [according to the risk of transplant rejection (see table 1 above)] in CD8-depleted versus unmanipulated groups. [ Time Frame: 1-year ] [ Designated as safety issue: No ]
  • T cell (CD3) and myeloid (CD13) chimerism in CD8-depleted versus unmanipulated groups. [ Time Frame: 1-year and then long term ] [ Designated as safety issue: No ]
  • Quality and timing of immune reconstitution in CD8-depleted versus unmanipulated groups. [ Time Frame: 1-year ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: March 2002
Study Completion Date: May 2008
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Unmanipulated PBSC
Procedure: Unmanipulated PBSC after nonmyeloablative conditioning

Conditioning regimen with 2 Gy TBI with or without added fludarabine (90 mg/m2).

Unmanipulated PBSC from HLA-identical sibling or HLA-matched related or unrelated donor

Experimental: 2
CD8-Depleted PBSC
Procedure: CD8-depleted PBSC after nonmyeloablative conditioning
Other Names:
  • Conditioning regimen with 2 Gy TBI with or without added fludarabine (90 mg/m2).
  • CD8-depleted PBSC from HLA-identical sibling or HLA-matched related or unrelated donor

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  1. Patients

    1.1. Diseases

    Malignant diseases confirmed histologically and not rapidly progressing:

    • Hematologic malignancies
    • AML;
    • ALL;
    • CML and other myeloproliferative disorders;
    • MDS;
    • Multiple myeloma;
    • CLL;
    • Non-Hodgkin's lymphoma;
    • Hodgkin's disease.
    • Non-hematologic malignancies
    • Renal cell carcinoma (metastatic).

    1.2. Inclusion criteria

    • Male or female; female patients must use a reliable contraception method;
    • Age lower than 70 yrs (family donor) or lower than 65 yrs (unrelated donor);
    • HIV negative;
    • No terminal organ failure;
    • No uncontrolled infection, arrhythmia or hypertension;
    • Family donor (HLA-identical) or unrelated donor (matched for A-B by low resolution typing and for DRB1-DQB1 by high resolution typing);
    • No previous radiation therapy precluding the use of 2 Gy TBI
    • Informed consent given by patient or his/her guardian if of minor age.

    1.3. Clinical situations

    • Theoretical disease indication for a standard allo-transplant, but not feasible because:
    • Age > 55 yrs;
    • Unacceptable end organ performance;
    • Patient's refusal.
    • Indication for a standard auto-transplant:

      • perform mini-allotransplantation 2-6 months after standard autotransplant.
    • Not an indication for intensification but a potential candidate for cellular immunotherapy.
  2. Donors

2.1. Inclusion criteria

  • Related to the recipient (sibling, parent or child) or unrelated;
  • Male or female;
  • Weight > 15 Kg (because of leukapheresis);
  • HIV negative;
  • No major contraindication for allogeneic PBSC donation by generally accepted criteria;
  • Informed consent given by donor or his/her guardian if of minor age.

2.2. Exclusion criteria

  • Any condition not fulfilling inclusion criteria;
  • Unable to undergo leukapheresis because of poor vein access or other reasons.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00693927

Locations
Belgium
CHU Sart Tilman
Liege, Belgium, B4000
Sponsors and Collaborators
University Hospital of Liege
Investigators
Study Chair: Yves Beguin, MD, PhD University of Liège
  More Information

No publications provided

Responsible Party: Yves Beguin, Prof, University Hospital of Liege
ClinicalTrials.gov Identifier: NCT00693927     History of Changes
Other Study ID Numbers: Minitransplant - random
Study First Received: May 29, 2008
Last Updated: September 1, 2011
Health Authority: Belgium: Institutional Review Board

Keywords provided by University Hospital of Liege:
Hematopoietic cell transplantation
Allogeneic
Nonmyeloablative
CD8-depletion
PBSC
GVHD
Hematological malignancies and renal cell carcinoma

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Fludarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014