Hematologic Malignancies
Conditions
Keywords
Hematopoietic cell transplantation, Allogeneic, Nonmyeloablative, CD8-depletion, PBSC, GVHD, Hematological malignancies and renal cell carcinoma
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.
Interventions
PROCEDUREUnmanipulated 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
PROCEDURECD8-depleted PBSC after nonmyeloablative conditioning
Sponsors
University of Liege
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 70 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
Belgium
Outcome results
None listed