Clinical trial NCT00693927: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematologic Malignancies
Keywords: Hematopoietic cell transplantation
Allogeneic
Nonmyeloablative
CD8-depletion
PBSC
GVHD
Hematological malignancies and renal cell carcinoma
Lead sponsor: University of Liege
Sponsor class: OTHER
First posted: 2008-06-09
Enrollment: 54
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of acute GVHD in CD8-depleted versus unmanipulated groups
timeFrame: 180 days
measure: Incidence of chronic GVHD (overall and extensive) in CD8-depleted versus unmanipulated groups.
timeFrame: 1-year
Secondary outcomes:
measure: Incidence of graft rejection [according to the risk of transplant rejection (see table 1 above)] in CD8-depleted versus unmanipulated groups.
timeFrame: 1-year
measure: T cell (CD3) and myeloid (CD13) chimerism in CD8-depleted versus unmanipulated groups.
timeFrame: 1-year and then long term
measure: Quality and timing of immune reconstitution in CD8-depleted versus unmanipulated groups.
timeFrame: 1-year
Other outcomes:
Locations:
city: Liege
country: Belgium
facility: CHU Sart Tilman
Study officials:
affiliation: University of Liege
name: Yves Beguin, MD, PhD
role: STUDY_CHAIR
References: