Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer
|ClinicalTrials.gov Identifier: NCT00027820|
Recruitment Status : Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : December 13, 2017
|Condition or disease||Intervention/treatment||Phase|
|Adult Acute Myeloid Leukemia in Remission Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Myelodysplastic Syndrome Childhood Renal Cell Carcinoma Chronic Myelomonocytic Leukemia Clear Cell Renal Cell Carcinoma de Novo Myelodysplastic Syndrome Metastatic Renal Cell Cancer Previously Treated Myelodysplastic Syndrome Progression of Multiple Myeloma or Plasma Cell Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Hodgkin Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult Non-Hodgkin Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Non-Hodgkin Lymphoma Refractory Anemia Refractory Anemia With Ringed Sideroblasts Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Renal Medullary Carcinoma Type 1 Papillary Renal Cell Carcinoma Type 2 Papillary Renal Cell Carcinoma Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia Untreated Childhood Acute Lymphoblastic Leukemia||Drug: Fludarabine Phosphate Radiation: Total-Body Irradiation Procedure: Peripheral Blood Stem Cell Transplantation Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Drug: Cyclosporine Drug: Mycophenolate Mofetil||Phase 1 Phase 2|
I. To determine whether stable unrelated peripheral blood stem cell (PBSC) grafts can be safely established using nonmyeloablative pretransplant conditioning with intensified post-grafting immunosuppression and with every (q) 8 hours (hr) and possibly q 6 hr mycophenolate mofetil (MMF) dosing in patients with hematologic malignancies and renal cell carcinoma.
II. To determine if the incidence and severity of acute grades II-IV graft-versus-host disease (GVHD) can be reduced in patients with sustained engraftment with the use of q 8 hr MMF dosing.
I. To determine if engraftment can be maintained in patients with low chimerism and high risk of rejection with the use of a single dose of fludarabine (fludarabine phosphate) followed by donor lymphocyte infusion (DLI) on continued MMF/cyclosporine (CSP).
II. To compare survival and disease free survival to those achieved under protocol 1463.
REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4, -3, and -2 and undergo total-body irradiation (TBI) on day 0.
TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO every 8 hours on days 0-40 with taper to day 96.
After completion of study treatment, patients are followed up at 6 months, 1 year, 1.5 years, 2 years, and then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||106 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Low-Dose TBI and Fludarabine Followed by Nonmyeloablative Unrelated Donor Peripheral Blood Stem Cell Transplantation Using Enhanced Postgrafting Immunosuppression for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-center Trial|
|Study Start Date :||August 2001|
|Actual Primary Completion Date :||September 2004|
Experimental: Treatment (PBSCT)
REDUCED-INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV on days -4, -3, and -2 and undergo TBI on day 0.
TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO every 8 hours on days 0-40 with taper to day 96.
Drug: Fludarabine Phosphate
Other Names:Radiation: Total-Body Irradiation
Other Names:Procedure: Peripheral Blood Stem Cell Transplantation
Undergo nonmyeloablative PBSCT
Other Names:Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo nonmyeloablative PBSCT
Other Names:Drug: Cyclosporine
Other Names:Drug: Mycophenolate Mofetil
- Risk of true graft rejection in patients with and without preceding chemotherapy [ Time Frame: Up to 5 years ]The goal is to reduce the risk in patients without preceding chemotherapy to < 20% and with preceding chemotherapy to < 10%.
- Risk of grades II-IV acute GVHD in those patients with sustained engraftment [ Time Frame: Up to 5 years ]The goal is to reduce the incidence of grades II-IV acute GVHD from 50% to less than 35% in patients with sustained engraftment by increasing the dosing of MMF to every 8 hours. The impact of the enhanced post-grafting immunosuppression on objective measures of GVHD will be described. These include doses and duration of immunosuppression (in particular corticosteroids) and number of GVHD treatment regimens used within the first year. These parameters will be compared to the results of protocol 1463.
- Incidence of reversing impending graft rejection (less than 40% donor cluster of differentiation [CD]3+ T cell chimerism) [ Time Frame: Up to 5 years ]The secondary objective of reversing pending graft rejection with fludarabine phosphate and DLI will be evaluated in the context of overall engraftment. The number of patients given DLI in this context is expected to be small. The response to DLI will be followed and reported in a descriptive manner. The effect of this intervention on adverse outcomes will be followed.
- Overall survival [ Time Frame: Up to 5 years ]
- Progression-free survival [ Time Frame: Up to 5 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00027820
|United States, Arizona|
|University of Arizona Health Sciences Center|
|Tucson, Arizona, United States, 85724|
|United States, California|
|Stanford University Hospitals and Clinics|
|Stanford, California, United States, 94305|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|United States, Texas|
|Baylor Medical Center at Garland|
|Garland, Texas, United States, 75042|
|United States, Utah|
|Huntsman Cancer Institute/University of Utah|
|Salt Lake City, Utah, United States, 84112|
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|United States, Wisconsin|
|Froedtert and the Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Leipzig, Germany, D-04103|
|University of Torino|
|Torino, Italy, 10126|
|Principal Investigator:||Brenda Sandmaier||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|