T-Cell Depletion, Donor Hematopoietic Stem Cell Transplant (HSCT), and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases
|ClinicalTrials.gov Identifier: NCT00589602|
Recruitment Status : Terminated (slow accrual)
First Posted : January 9, 2008
Results First Posted : May 30, 2017
Last Update Posted : May 30, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Malignant Plasma Cell Neoplasms Myelodysplastic Syndromes Precancerous/Nonmalignant Condition Secondary Myelofibrosis||Procedure: peripheral blood lymphocyte therapy Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation (TBI)||Phase 2|
- 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 peripheral blood progenitor cell (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 matched unrelated donor (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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Allogeneic Hematopoietic Stem Cell Transplantation|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||January 2004|
|Actual Primary Completion Date :||August 2009|
|Actual Study Completion Date :||December 2014|
Experimental: T-Cell Depletion Transplant
Our protocol is designed to attempt to improve the current results of matched unrelated donor (MUD) allo bone marrow transplant (BMT) and will be a major step towards the introduction and refinement of graft engineering. Our approach will address in a rational fashion all major technical and clinical aspects of MUD allo BMT.
Peripheral blood lymphocyte therapy; cyclophosphamide, tacrolimus, peripheral blood stem cell transplantation; total-body irradiation; 'allogeneic hematopoietic stem cell transplantation'
Procedure: peripheral blood lymphocyte therapy
T-cell depletion will be accomplished using CD34 selection with the Baxter Isolex 300i v. 2.5 device. The desirable T-cell dose will be >0.5 x 105 but <1.0 x 105 CD3+ cells per kg. The targeted CD34 cell dose will be >2 x 106 cells/kg.
Other Name: T-cell depletionProcedure: allogeneic hematopoietic stem cell transplantation
Allogeneic Hematopoietic Stem Cell TransplantationProcedure: peripheral blood stem cell transplantation
Peripheral blood stem cell transplantationRadiation: total-body irradiation (TBI)
Treatment will be delivered using 6MV photons twice daily for 3 days
- Treatment-related Mortality (TRM) [ Time Frame: 180 days after transplant ]The complication rate in matched unrelated donor (MUD) allogeneic bone marrow transplant (allo BMT) is known to be high. Graft failure and severe graft versus host disease (GvHD) are the most significant contributors to treatment related mortality (TRM). This treatment regimen will be considered unacceptable if the number of patients that experience TRM is 55% or greater, and effective if TRM is 33% or less.
- The Rate of Acute Graft Versus Host Disease (GVHD) [ Time Frame: D+100 from transplant ]
- Number of Participants With Duration of Absolute Neutropenia [ Time Frame: D+100 from transplant ]
- Number of Participants Able to Receive T-cell Add Backs [ Time Frame: through D+100 ]Patients receive defined doses of donor T cells by IV infusion on days 45 and 100, in absence of active graft-versus-host disease (GVHD) requiring steroids.
- Number of Participants With Relapse-free Survival [ Time Frame: after 7 years of follow up ]number of patients that were still alive and relapse free
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00589602
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Study Chair:||Brian J. Bolwell, MD||The Cleveland Clinic|
|Principal Investigator:||Jarek Maciejewski, MD, PhD||The Cleveland Clinic|