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A Phase II Trial of Total Body Irradiation Plus Metabolism-Based Cyclophosphamide Dosing as Preparative Therapy for Allogeneic Hematopoietic Cell Transplant for Patients With Hematological Malignancy
RATIONALE: Giving total-body irradiation and chemotherapy, such as cyclophosphamide, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of cancer or abnormal cells. When the 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 immunosuppressive therapy before or after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving total-body irradiation together with cyclophosphamide works in treating patients who are undergoing donor stem cell transplant for hematologic cancer and other diseases.
OBJECTIVES: Primary * Evaluate the potential efficacy of targeting cyclophosphamide to a metabolic endpoint when given together with total-body irradiation, in terms of day 200 nonrelapse mortality, in patients with hematologic cancer and other diseases who are undergoing allogeneic hematopoietic stem cell transplantation. Secondary * Determine the overall survival of patients treated with this regimen. * Determine the rate of relapse in patients treated with this regimen. * Determine the occurrence of sinusoidal obstruction syndrome in patients treated with this regimen. * Determine the occurrence of acute renal failure in these patients. * Determine the occurrence of respiratory failure in these patients. OUTLINE: * Conditioning regimen: Patients undergo total-body irradiation twice daily on days -6 to -4. Patients also receive cyclophosphamide IV over 1 hour on day -3 and then IV at a metabolism-based dose\* on day -2. NOTE: \*Patients undergo frequent blood sampling after completion of the first cyclophosphamide infusion for pharmacokinetic studies in order to determine the dose for the second cyclophosphamide infusion. * Allogeneic stem cell transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. * Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis as per the attending physician, including one of the following regimens: cyclosporine and methotrexate; tacrolimus and methotrexate; tacrolimus and mycophenolate mofetil; or sirolimus, tacrolimus, and methotrexate (as per the GVHD prophylaxis regimen chosen for each patient). After completion of study treatment, patients are followed periodically for at least 200 days. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Age
18 - 70 years
Sex
ALL
Healthy Volunteers
No
Seattle Cancer Care Alliance
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Start Date
May 1, 2005
Primary Completion Date
November 1, 2007
Last Updated
May 7, 2010
50
ESTIMATED participants
cyclophosphamide
DRUG
cyclosporine
DRUG
methotrexate
DRUG
mycophenolate mofetil
DRUG
sirolimus
DRUG
tacrolimus
DRUG
pharmacological study
OTHER
allogeneic bone marrow transplantation
PROCEDURE
allogeneic hematopoietic stem cell transplantation
PROCEDURE
peripheral blood stem cell transplantation
PROCEDURE
total-body irradiation
RADIATION
Lead Sponsor
Fred Hutchinson Cancer Center
Collaborators
NCT06285890
NCT06311227
Data Source & Attribution
This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.
Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.
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View ClinicalTrials.gov Terms and ConditionsNCT05139017