T-Cell Depletion, Donor HSCT, and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases (6501)
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help destroy any remaining cancer cells (graft-versus-tumor effect).
PURPOSE: This phase II trial is studying T-cell depletion in donor stem cell transplant followed by delayed T cell infusions in treating patients with hematologic cancer or other disease.
Chronic Myeloproliferative Disorders
Multiple Myeloma and Malignant Plasma Cell Neoplasms
Biological: peripheral blood lymphocyte therapy
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Feasibility Study of T-Cell Depletion in Allogeneic Unrelated Bone Marrow Transplantation (MUD ALLO BMT) Followed by Delayed T-Cell Infusions|
- Treatment-related mortality (TRM) [ Time Frame: TRM ] [ Designated as safety issue: Yes ]
- The rate and severity of acute GVHD [ Time Frame: Relapse and survival ] [ Designated as safety issue: Yes ]
- Duration of absolute neutropenia [ Time Frame: Relapse and survival ] [ Designated as safety issue: Yes ]
- Ability to receive T-cell add backs [ Time Frame: Relapse and Survival ] [ Designated as safety issue: No ]
- Relapse and relapse-free survival [ Time Frame: Relapse and survival ] [ Designated as safety issue: No ]
|Study Start Date:||January 2004|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
|No Intervention: Transplant Related Mortality||
Biological: peripheral blood lymphocyte therapy
Other Name: T-cell depletionDrug: cyclophosphamide
Other Name: T-cell depletionDrug: tacrolimus
Other Name: T-cell depletionProcedure: allogeneic hematopoietic stem cell transplantation
Other Name: T-cell depletionProcedure: peripheral blood stem cell transplantation
Other Name: T-cell depletionRadiation: total-body irradiation
Other Name: T-cell depletion
- Determine if T-cell depletion of a peripheral blood progenitor cell (PBPC) graft followed by delayed add-backs of defined doses of donor lymphocytes decreases the rate of graft-versus-host disease and its complications in matched unrelated donor (MUD) allogeneic PBPC transplantation in patients with hematologic cancers or other diseases.
- Determine whether targeted T-cell dosages in the PBPC graft can be achieved in these patients by positive CD34+ selection using the Baxter Inc. Isolex 300i v. 2.5.
- Determine the effects of T-cell depletion on the rate of engraftment in these patients.
- Develop a MUD allogeneic transplantation regimen that will decrease overall treatment-related mortality in these patients.
OUTLINE: This is a non-randomized study.
- Myeloablative preparative regimen: Patients receive cyclophosphamide IV once daily on days -5 and -4 followed by total body irradiation twice daily on days -3, -2, and -1. Patients also receive tacrolimus on day -1 administered by continuous IV infusion over 24 hours.
- Peripheral blood progenitor cell graft transplantation: Patients receive T-cell depleted, peripheral blood progenitor cells (PBPC) by IV infusion on day 0. Beginning 1 day after completion of the PBPC infusion, patients receive filgrastim (G-CSF) subcutaneously once daily until blood counts recover.
- Post transplantation T cell add-backs: Patients receive defined doses of donor T cells by IV infusion on days 45 and 100, in the absence of active graft-versus-host disease (GVHD) requiring steroids*.
NOTE: *A T cell add-back may be given in the presence of GVHD, if the investigator considers the risk from relapse or overwhelming viral infection to outweigh the risk of exacerbating GVHD.
Patients will be followed periodically for relapse and survival.
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Study Chair:||Brian J. Bolwell, MD||The Cleveland Clinic|