Optimized Cord Blood Transplantation for the Treatment of High-Risk Hematologic Malignancies in Adults and Pediatrics

Fred Hutchinson Cancer Center1 site in 1 country54 target enrollmentJuly 23, 2024

InterventionsBone Marrow Aspirate Echocardiography Biospecimen Collection Cyclophosphamide Cyclosporine Diagnostic Imaging Fludarabine Phosphate Multigated Acquisition Scan Mycophenolate Mofetil Survey Administration Total-Body Irradiation Umbilical Cord Blood Transplantation Thiotepa

DrugsCyclophosphamide Cyclosporine Fludarabine Phosphate Mycophenolate Mofetil Thiotepa

Overview

Phase: Phase 2
Intervention: Bone Marrow Aspirate
Conditions: Not specified
Sponsor: Fred Hutchinson Cancer Center
Enrollment: 54
Locations: 1
Primary Endpoint: Overall survival
Status: Recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

July 23, 2024

End Date

October 31, 2032

Last Updated

3 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Fred Hutchinson Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients aged 6 months to =\< 65 years at time of consent.
•Acute myelogenous leukemia (AML):
•Complete first remission (CR1), complete second remission (CR2) or greater (CR2+), must have \< 5% marrow blasts at the time of transplant.
•Patients in morphologic remission with persistent cytogenetic, flow cytometric, or molecular aberrations are eligible.
•Acute lymphoblastic leukemia (ALL):
•Complete first remission (CR1) at high risk for relapse such as any of the following:
•Presence of any high-risk cytogenetic abnormalities such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23) or other high-risk molecular abnormality.
•Failure to achieve MRD- complete remission after induction therapy.
•Persistence or recurrence of minimal residual disease on therapy.
•Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.

Exclusion Criteria

•Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis.
•Patients persistent with central nervous system (CNS) involvement in cerebrospinal fluid (CSF) or CNS imaging at time of screening0
•Prior checkpoint inhibitors/ blockade in the last 12 months.
•Two prior stem cell transplants of any kind.
•One prior autologous stem cell transplant within the preceding 12 months.
•Prior allogeneic transplantation.
•Prior involved field radiation therapy that would preclude safe delivery of 400cGy total body irradiation (TBI) in the opinion of radiation oncology.
•Active and uncontrolled infection at time of transplantation.
•HIV infection.
•Inadequate performance status/ organ function.

Intervention: Total-Body Irradiation

Arm II (myeloablative UCBT)

See detailed description.

Intervention: Umbilical Cord Blood Transplantation

Outcomes

Primary Outcomes

Overall survival

Time Frame: At 1 year

Will be assessed after optimized cord blood transplant (CBT) in adults and children with hematologic malignancies. Will be calculated using the Kaplan-Meier method.

Secondary Outcomes

Incidence of grade II-IV and III-IV aGVHD(At day 180)
Incidence of chronic graft-versus-host disease (cGVHD)(At 1, 2 and 3 years)
Time to immunosuppression cessation(Up to 1 year)
Incidence of grade II-IV and III-IV acute graft-versus-host disease (aGVHD)(At day 100)
Cumulative incidence of neutrophil and platelet engraftment(Up to 1 year)
Incidences of graft failure(Up to 1 year)
Pattern of donor chimerism(Up to 1 year)
Incidence of pre-engraftment syndrome (PES)(Up to 1 year)
Incidence of relapse(At 1, and 2 years after CBT)
Organ distribution of GVHD(Up to 1 year)
Incidence of adverse events(Up to 1 year)
Incidence of transplant related mortality (TRM)(At 100 days, 6 months, 1 and 2 years)