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

Hematologic Malignancies Clinical Trial

Official title:

Nonmyeloablative Stem Cell Transplantation With CD8-depleted or Unmanipulated Peripheral Blood Stem Cells: A Prospective Randomized Phase II Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00693927
• Other study ID #: Minitransplant - random
• Status: Completed
• Phase: Phase 2
• First received: May 29, 2008
• Last updated: September 1, 2011
• Start date: March 2002
• Est. completion date: May 2008

Study information

• Verified date: September 2011
• Source: University Hospital of Liege
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: May 2008
• Est. primary completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematologic Malignancies

Intervention

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
• CD8-depleted PBSC after nonmyeloablative conditioning

Locations

Country	Name	City	State
Belgium	CHU Sart Tilman	Liege

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital of Liege

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of acute GVHD in CD8-depleted versus unmanipulated groups		180 days	No
Primary	Incidence of chronic GVHD (overall and extensive) in CD8-depleted versus unmanipulated groups.		1-year	No
Secondary	Incidence of graft rejection [according to the risk of transplant rejection (see table 1 above)] in CD8-depleted versus unmanipulated groups.		1-year	No
Secondary	T cell (CD3) and myeloid (CD13) chimerism in CD8-depleted versus unmanipulated groups.		1-year and then long term	No
Secondary	Quality and timing of immune reconstitution in CD8-depleted versus unmanipulated groups.		1-year	No