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

Primary Purpose

Hematologic Malignancies

Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Unmanipulated PBSC after nonmyeloablative conditioning
CD8-depleted PBSC after nonmyeloablative conditioning
Sponsored by
University of Liege
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring Hematopoietic cell transplantation, Allogeneic, Nonmyeloablative, CD8-depletion, PBSC, GVHD, Hematological malignancies and renal cell carcinoma

Eligibility Criteria

undefined - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

  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.

Sites / Locations

  • CHU Sart Tilman

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

1

2

Arm Description

Unmanipulated PBSC

CD8-Depleted PBSC

Outcomes

Primary Outcome Measures

Incidence of acute GVHD in CD8-depleted versus unmanipulated groups
Incidence of chronic GVHD (overall and extensive) in CD8-depleted versus unmanipulated groups.

Secondary Outcome Measures

Incidence of graft rejection [according to the risk of transplant rejection (see table 1 above)] in CD8-depleted versus unmanipulated groups.
T cell (CD3) and myeloid (CD13) chimerism in CD8-depleted versus unmanipulated groups.
Quality and timing of immune reconstitution in CD8-depleted versus unmanipulated groups.

Full Information

First Posted
May 29, 2008
Last Updated
September 1, 2011
Sponsor
University of Liege
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1. Study Identification

Unique Protocol Identification Number
NCT00693927
Brief Title
Nonmyeloablative Stem Cell Transplantation With CD8-depleted or Unmanipulated Peripheral Blood Stem Cells (PBSC)
Official Title
Nonmyeloablative Stem Cell Transplantation With CD8-depleted or Unmanipulated Peripheral Blood Stem Cells: A Prospective Randomized Phase II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2011
Overall Recruitment Status
Completed
Study Start Date
March 2002 (undefined)
Primary Completion Date
May 2005 (Actual)
Study Completion Date
May 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Liege

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancies
Keywords
Hematopoietic cell transplantation, Allogeneic, Nonmyeloablative, CD8-depletion, PBSC, GVHD, Hematological malignancies and renal cell carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Unmanipulated PBSC
Arm Title
2
Arm Type
Experimental
Arm Description
CD8-Depleted PBSC
Intervention Type
Procedure
Intervention Name(s)
Unmanipulated PBSC after nonmyeloablative conditioning
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
CD8-depleted PBSC after nonmyeloablative conditioning
Other Intervention Name(s)
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
Primary Outcome Measure Information:
Title
Incidence of acute GVHD in CD8-depleted versus unmanipulated groups
Time Frame
180 days
Title
Incidence of chronic GVHD (overall and extensive) in CD8-depleted versus unmanipulated groups.
Time Frame
1-year
Secondary Outcome Measure Information:
Title
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
Title
T cell (CD3) and myeloid (CD13) chimerism in CD8-depleted versus unmanipulated groups.
Time Frame
1-year and then long term
Title
Quality and timing of immune reconstitution in CD8-depleted versus unmanipulated groups.
Time Frame
1-year

10. Eligibility

Sex
All
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yves Beguin, MD, PhD
Organizational Affiliation
University of Liege
Official's Role
Study Chair
Facility Information:
Facility Name
CHU Sart Tilman
City
Liege
ZIP/Postal Code
B4000
Country
Belgium

12. IPD Sharing Statement

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

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