This phase II trial is studying how well umbilical cord blood transplant from a donor works in treating patients with hematological cancer. Giving chemotherapy and total-body irradiation (TBI) before a donor umbilical cord blood 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 the healthy stem cells from an unrelated donor, that do not exactly match the patient's blood, 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 (called graft-versus-host disease). Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.
PRIMARY OBJECTIVES: I. Estimate probability of one year survival. II. Demonstrate equivalent or improved engraftment rates with a non-anti-thymocyte globulin (ATG) based conditioning regimen. Patients will be considered graft failure/rejections provided they meet any of the criteria listed below: * Absence of 3 consecutive days with neutrophils \>= 500/ul combined with host cluster of differentiation (CD)3 peripheral blood chimerism \>= 50% at day 42 * Absence of 3 consecutive days with neutrophils \>= 500/ul under any circumstances at day 55 * Death after day 28 with neutrophil count \< 100/ul without any evidence of engraftment (\< 5% donor CD3) * Primary autologous count recovery with \< 5% donor CD3 peripheral blood chimerism at count recovery and without relapse SECONDARY OBJECTIVES: I. Six month non-relapse mortality. II. Overall incidence of graft failure/rejection. Patients will be considered graft failure/rejections provided they meet any of the criteria listed below: * Absence of 3 consecutive days with neutrophils \>= 500/ul combined with host CD3 peripheral blood chimerism \>= 50% at day 42 * Absence of 3 consecutive days with neutrophils \>= 500/ul under any circumstances at day 55 * Death after day 28 with neutrophil count \< 100/ul without any evidence of engraftment (\< 5% donor CD3) * Primary autologous count recovery with \< 5% donor CD3 peripheral blood chimerism at count recovery and without relapse III. Kinetics of chimeric reconstitution. IV. Incidence of neutrophil engraftment by day 42. V. Incidence of platelet engraftment by six months. VI. Incidence of grade II-IV and III-IV acute graft-versus-host disease (GvHD) at day 100. VII. Incidence of one year chronic GvHD. VIII. Incidence of clinically significant infections at 6 months, 1 year, 2 years. IX. Probability of one and two year survival. X. Incidence of one and two year relapse or disease progression. XI. Fred Hutchinson Cancer Research Center (FHCRC) patients: Kinetics of immune reconstitution, with both functional and quantitative assays. XII. FHCRC patients: Examination of possible immunologic factors leading to emergence of a dominant unit. OUTLINE: CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6. Patients undergo a lower dose of total-body irradiation (TBI) on day -1. UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0. IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to +180 and mycophenolate mofetil IV or orally (PO) every 8 hours on days 0 to +96. After completion of study treatment, patients are followed periodically for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
73
Undergo umbilical cord blood transplant
Given IV
Given IV
Given IV
Correlative studies
Given IV or PO
Undergo TBI
Undergo umbilical cord blood transplant
University of Colorado Hospital
Aurora, Colorado, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
LDS Hospital
Salt Lake City, Utah, United States
VA Puget Sound Health Care System
Seattle, Washington, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Overall Survival
Kaplan-Meier and cumulative incidence estimates will be used.
Time frame: At 1 year
Median Time to ANC > 500
Time frame: By day 55
Number of Participants With Graft Failure/Rejection
descriptive
Time frame: By day 55
Time to Platelet Engraftment of > 20,000 Cells Per mm3
median and range
Time frame: By 6 months
Percent of Patients With Grade II-IV Acute Graft Versus Host Disease
Chi-square test was used to determine percent of grade II-IV GVHD using Glucksberg criteria
Time frame: By day 100
Percent of Patients With Acute GVHD Grades III-IV
Fischer's exact test was used to determined percent of patients with acute grade III-IV GVHD by Glucksberg criteria
Time frame: 100 days
Percent of Patients With Chronic GVHD
Kaplan-Meier and cumulative incidence estimates will be used to measure percent of patients with chronic GVHD by NIH consensus criteria.
Time frame: At 2 years
Percent of Patients With Non-relapse Mortality
Kaplan-Meier and cumulative incidence estimates
Time frame: 6 months
Percent of Patients With Non-relapse Mortality
Kaplan-Meier and cumulative incidence estimates
Time frame: 1 year
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