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

Sponsor

University of Liege (Other)

Overall Status

Completed

CT.gov ID

NCT00693927

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Mar 1, 2002

Actual Primary Completion Date :

May 1, 2005

Actual Study Completion Date :

May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Incidence of acute GVHD in CD8-depleted versus unmanipulated groups [180 days]
Incidence of chronic GVHD (overall and extensive) in CD8-depleted versus unmanipulated groups. [1-year]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.