RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). PURPOSE: This phase I trial is studying the safety of donor umbilical cord blood transplant after fludarabine phosphate, cyclophosphamide, and total-body irradiation in treating patients with high-risk hematologic cancer (now closed). The Phase II part of this trial is studying whether priming one of two UCB units with C3a facilitates engraftment of the treated unit.
OUTLINE: * Nonmyeloablative preparative regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6. Patients then undergo total-body irradiation on day -1. Some patients also receive anti-thymocyte globulin IV every 12 hours on days -6, -5, and -4. * Umbilical cord blood (UCB) transplantation: Patients undergo unmanipulated UCB transplantation followed by complement 3a fragment primed UCB transplantation on day 0. Treatment for graft-vs-host disease prophylaxis is also given. After completion of study therapy, patients are followed up periodically for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
50 mg/kg intravenously (IV) over 2 hours on Day -6.
40 mg/m\^2 over 1 hour on Days -6 through -2.
200 cGy on Day -1
On Day 0, the C3a primed UCB unit will be infused intravenously SECOND, within 30 minutes of the completion of the infusion of the unmanipulated UCB unit, through a central line without in-line filtration in a manner identical to the unmanipulated UCB unit.
On Day 0, the unmanipulated UCB unit will be infused FIRST through a central line without in-line filtration per institutional guidelines.
University of Minnesota Medical Center - Fairview
Minneapolis, Minnesota, United States
Number of Patients With the Complement 3a (C3a) Unit Predominating
Efficacy of the pre-incubation of one of two umbilical cord blood (UCB) units with C3a as part of a unrelated donor double UCB nonmyeloablative transplantation in patients with high-risk hematological malignancies.
Time frame: Day 180
Neutrophil Engraftment
Achieving 500 neutrophils/uL by day 42.
Time frame: Day 42
Donor Chimerism in Blood
Percentage of donor DNA present in the peripheral blood
Time frame: Day 28
Incidence of Grades II-IV Graft-vs-host Disease
Development of graft-versus-host disease through day 100.
Time frame: Day 0 through Day 100
Non-Relapse Mortality
Deaths not due to relapse.
Time frame: Day 180
Overall Survival
Survival (alive) from transplantation to last follow-up.
Time frame: Day 360
Bone Marrow Chimerism
Percentage of donor DNA in the bone marrow.
Time frame: Day 21
Chronic Graft-Versus-Host Disease
Patients who developed chronic graft-versus-host disease.
Time frame: Day 360
Relapse of Disease
Patients who developed disease relapse after transplantation.
Time frame: Day 360
Disease Progression
Patients who developed disease progression after transplantation.
Time frame: Day 360
Platelet Recovery
Number of patients with \>20,000 platelets/uL by day 180
Time frame: Day 180
Donor Chimerism in Blood
Percentage of donor DNA present in the peripheral blood
Time frame: Day 60
Incidence of Grades III-IV Graft-vs-host Disease
Development of graft-versus-host disease by day 100.
Time frame: 0 to 100 days
Non-relapse Mortality
Deaths not due to relapse.
Time frame: Day 360
Overall Survival at Day 720
Survival (alive) from transplantation to last follow-up at day 720.
Time frame: 720 days
Relapse of Disease
Patients who developed disease relapse after transplantation.
Time frame: Day 720
Disease Progression
Patients who developed disease progression after transplantation.
Time frame: Day 720
Donor Chimerism
Percentage of donor DNA in the bone marrow.
Time frame: Day 100
Donor Chimerism
Percentage of donor DNA in the bone marrow.
Time frame: Day 180
Donor Chimerism
Percentage of donor DNA in the bone marrow.
Time frame: Day 360
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