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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hematologic Malignancies

Intervention / Treatment
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* Procedure: Unmanipulated PBSC after nonmyeloablative conditioning
* Procedure: CD8-depleted PBSC after nonmyeloablative conditioning


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Unmanipulated PBSC | Procedure: Unmanipulated PBSC after nonmyeloablative conditioning<br>* 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<br>|
| Experimental: 2<br>CD8-Depleted PBSC | Procedure: CD8-depleted PBSC after nonmyeloablative conditioning<br> <br> * Other names: CD8-depleted PBSC from HLA-identical sibling or HLA-matched related or unrelated donor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic cell transplantation, Allogeneic, Nonmyeloablative, CD8-depletion, PBSC, GVHD, Hematological malignancies and renal cell carcinoma