This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating patients with hematologic diseases. Giving chemotherapy, such as cyclophosphamide, fludarabine and thiotepa, and TBI before a donor cord blood transplant (CBT) 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 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 cyclosporine and mycophenolate mofetil after transplant may stop this from happening in patients with high-risk hematologic diseases.
OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: Patients aged 6 months through 30 years old receive myeloablative conditioning comprising fludarabine intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 and -6, and undergo high-dose TBI twice daily (BID) on days -4 to -1. Patients then undergo UCBT on day 0. Patients undergo blood sample collection throughout the study. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and diagnostic imaging during screening and as clinically indicated on study. Patients also undergo blood sample collection throughout the study and bone marrow aspirate during screening and on study. ARM II: Patients aged 6 months through 65 years old receive myeloablative conditioning comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI once daily (QD) on days -2 and -1. Patients undergo ECHO or MUGA and diagnostic imaging during screening and as clinically indicated on study. Patients also undergo blood sample collection throughout the study and bone marrow aspirate during screening and on study. All patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine orally (PO) (if tolerated), on days -3 to 100 with taper on day 101. Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if tolerated) three times daily (TID) on days 8-30. Mycophenolate mofetil is tapered to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred \> day 30) after engraftment if there continues to be no evidence of acute GVHD. After completion of study treatment, patients are followed up at day 180, 1 year, and 2 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Undergo blood sample collection
Undergo bone marrow aspirate
Receive IV
Receive IV or PO
Undergo diagnostic imaging
Undergo ECHO
Receive IV
Undergo MUGA
Receive IV
Ancillary studies
Receive IV
Undergo high-dose or middle-intensity TBI
Undergo UCBT
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGOverall survival
Will be assessed after optimized cord blood transplant (CBT) in adults and children with hematologic malignancies. Will be calculated using the Kaplan-Meier method.
Time frame: At 1 year
Cumulative incidence of neutrophil and platelet engraftment
Will be calculated within the competing risks framework considering death without neutrophil or platelet recovery, respectively, as completing events
Time frame: Up to 1 year
Incidences of graft failure
Will be calculated within the competing risks framework considering death without engraftment before day 21 as a competing event.
Time frame: Up to 1 year
Incidence of grade II-IV and III-IV acute graft-versus-host disease (aGVHD)
Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.
Time frame: At day 100
Incidence of grade II-IV and III-IV aGVHD
Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.
Time frame: At day 180
Incidence of chronic graft-versus-host disease (cGVHD)
Will be calculated within the competing risks framework considering relapse/ death without developing GVHD, death in the absence of relapse, and relapse as competing events, respectively.
Time frame: At 1, 2 and 3 years
Organ distribution of GVHD
Will be calculated within the competing risks framework considering death without neutrophil or platelet recovery, respectively, as completing events
Time frame: Up to 1 year
Incidence of adverse events
Will be assessed using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0).
Time frame: Up to 1 year
Time to immunosuppression cessation
Will be assessed using CTCAE v 5.0.
Time frame: Up to 1 year
Pattern of donor chimerism
Will be assessed using CTCAE v 5.0.
Time frame: Up to 1 year
Incidence of pre-engraftment syndrome (PES)
Will be assessed using CTCAE v 5.0.
Time frame: Up to 1 year
Incidence of transplant related mortality (TRM)
Time frame: At 100 days, 6 months, 1 and 2 years
Incidence of relapse
Time frame: At 1, and 2 years after CBT
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