Donor Stem Cell Transplant in Treating Patients With Myeloid Cancer or Other Disease
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|ClinicalTrials.gov Identifier: NCT00392782|
Recruitment Status : Terminated
First Posted : October 26, 2006
Results First Posted : July 15, 2011
Last Update Posted : December 28, 2017
RATIONALE: Giving total-body irradiation and chemotherapy, such as fludarabine and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When healthy 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. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with myeloid cancer or other disease.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Myelodysplastic Syndromes||Biological: anti-thymocyte globulin Drug: fludarabine phosphate Drug: thiotepa Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation||Phase 2|
- Determine the incidence of disease-free survival at 1 year in patients with acute or chronic myeloid leukemias undergoing T-cell-depleted hematopoietic stem cell transplantation from HLA-C mismatched, unrelated donors.
- Determine the incidence of disease relapse at 1 year in patients treated with this regimen.
- Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days and chronic GVHD at 1 year in these patients.
- Determine the incidence of graft failure at day 100.
- Determine the transplant-related mortality of these patients at 1 year.
- Determine the overall survival of these patients at 1 year.
OUTLINE: This is a prospective, multicenter study. Patients are stratified according to killer-cell immunoglobulin-like receptors (KIR) epitope mismatch (yes [experimental] vs no [control]).
- Myeloablative preparative regimen: Patients undergo total body irradiation twice daily on days -10 and -9 and receive thiotepa intravenously (IV) over 4 hours on days -8 and -7, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and antithymocyte globulin IV over 4-6 hours on days -5 to -2.
- Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo filgrastim (G-CSF)-mobilized, T-cell-depleted, CD34+-selected allogeneic PBSC transplantation on day 0.
After completion of study treatment, patients are followed periodically for at least 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter, Prospective Trial to Evaluate the Role of NK Cell KIR Epitope Mismatch on Mortality and Disease Relapse in T-Cell Depleted Hematopoietic Stem Cell Transplantation From HLA-C Mismatched, Unrelated Donors for Myeloid Malignancies|
|Study Start Date :||July 2005|
|Actual Primary Completion Date :||May 2011|
|Actual Study Completion Date :||May 2011|
|Experimental: Natural Killer Cell Kir Epitope||
Biological: anti-thymocyte globulin
Rabbit thymoglobulin will be given intravenously at a dose of 2.5 mg/kg on days -5,-4, -3, and -2. The first dose of thymoglobulin will be given over six (6) hours and subsequent doses over four (4) or more hours as tolerated or, per institutional anti-thymocyte globulin (ATG) administration guidelines.
Other Name: ATGDrug: fludarabine phosphate
Fludarabine 40 mg/m^2/day intravenously (IV) over 30-60 minutes on days -7,-6,-5,-4,-3 (total dose 200 mg/m^2).
Other Name: FludaraDrug: thiotepa
Thiotepa 5 mg/kg/day intravenously (IV) over 4 hours on days -8, -7 (total dose 10 mg/kg).Procedure: peripheral blood stem cell transplantation
Peripheral Blood Stem Cell (PBSC) Infusion. All patients will receive granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC on day 0 (or day+1 when available) following CD34 cell selection for ex vivo T cell removal. PBSC is infused via a central venous catheter using blood infusion tubing.
Other Name: PBSCRadiation: total-body irradiation
The total-body irradiation (TBI) will be given in 2 fractions of 400 cGy each administered on day -10 and -9 via anterior and posterior fields for a total dose of 800 cGy.
Other Name: TBI
- Incidence of Disease-free Survival [ Time Frame: 1 Year ]Number of patients alive and without disease at 1 year after transplant.
- Incidence of Disease Relapse [ Time Frame: 1 Year ]Number of patients with disease at 1 year.
- Incidence of Grade II-IV Acute Graft-vs-host Disease (GVHD) [ Time Frame: Day 100 ]Number of patients with grade II-IV acute graft-versus-host disease at Day 100 post transplant. Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. Grade I=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening.
- Incidence of Chronic Graft-versus-host Disease (GVHD) [ Time Frame: 1 Year ]Number of patients with chronic graft-versus-host disease at 1 year post transplant. Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. Grade I=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening. Chronic GVHD is an extension of acute GVHD.
- Incidence of Graft Failure [ Time Frame: Day 100 ]Number of patients with graft failure is defined by lack of neutrophil engraftment by 100 days after transplant in patients surviving a minimum of 14 days.
- Transplant-related Mortality [ Time Frame: 1 Year ]Number of patients with treatment related death at 1 year post transplant.
- Overall Survival [ Time Frame: 1 Year ]Number of patients who were deceased at 1 year post transplant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00392782
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Georgia|
|Winship Cancer Institute of Emory University|
|Atlanta, Georgia, United States, 30322|
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202-5289|
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, Missouri|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis|
|Saint Louis, Missouri, United States, 63110|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210-1240|
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|United States, Wisconsin|
|Medical College of Wisconsin Cancer Center|
|Milwaukee, Wisconsin, United States, 53226|
|Midwest Children's Cancer Center at Children's Hospital of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Daniel J. Weisdorf, MD||Masonic Cancer Center, University of Minnesota|