The goal of this clinical trial is to see if adding abatacept to tacrolimus and MMF prevents or reduces the chances of acute graft versus host disease which is a complication that can occur after transplant in participants with blood cancer. The usual therapy for graft versus host disease prevention after a cord blood transplant includes tacrolimus and MMF. The main question this clinical trial aims to answer is whether or not abatacept will be safe and effective in reducing aGVHD rates in dCBT. Participants will: * Partake in exams, tests, and procedures as part of usual cancer care. * Partake in conditioning, which is the treatment that is given before a transplant. * Have a cord blood transplant. * Partake in radiation following the transplant.
Cord blood (CB) is a valuable alternative graft source for patients with hematologic malignancies in need of allogeneic transplantation who lack human leukocyte antigen (HLA)-matched adult donors. In Black, Asian, Hispanic populations, the chance of finding a HLA matched donor is 23%, 41%, and 46%, respectively. CB allows for greater HLA difference between donor and recipient, and increases the availability of donors, and therefore transplant, to these populations. Retrospective analyses and prospective trials demonstrate that recipients of double CB transplant (dCBT) have a grade II-IV acute graft versus host disease (aGVHD) rate of 45-90% and grade III-IV aGVHD rates up to 24%. This high aGVHD rate is likely due to the HLA-disparities between donor and recipient, which also drives a robust graft versus leukemia response8. Anti-thymocyte globin has been used in dCBT to reduce the incidence of aGVHD, but is no longer recommended due to delayed immune-reconstitution of the CB grafts. The ABA2 trial demonstrated efficacy and safety of abatacept as prophylaxis for aGVHD in HLA-mismatched unrelated donors (MMUD), significantly reducing the rate both of grade III-IV aGVHD and grade II-IV aGVHD in 7/8 MMUD when compared to historical controls. Our hypothesis is that abatacept will be safe and effective in reducing aGVHD rates in dCBT.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Cyclophosphamide (Cy) is one part of the conditioning regimen. 50 mg/kg beginning on day -6.
Fludarabine (Flu) is one part of the conditioning regimen. 150 mg/m2 (30 mg/m2 per day on days -6 to -2)
Thiotepa (Thio) is one part of the conditioning regimen.10 mg/kg (5 mg/kg per day on days -5 and -4)
400 cGy (200 cGy per day on days -2 and -1).
Cord blood is a regulated biologic. Selection of cord blood units will be based on published guidelines.
Tacrolimus will be administered post transplant. Graft-versus-host disease prophylaxis will consist of tacrolimus and mycophenolate mofetil (MMF), starting on day-5. Tacrolimus will continue at least until day 180 and then be tapered off.
MMF will be administered post transplant. Graft-versus-host disease prophylaxis will consist of tacrolimus and mycophenolate mofetil (MMF), starting on day-5. MMF will continue until day 30.
Abatacept at a dose of 10mg/kg will be given on days T-1, T+5, T+14 and T+28.
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
RECRUITINGSevere aGVHD free survival
To assess severe aGVHD (grade III-IV acute GVHD) free survival (SGFS) at T+180.
Time frame: 180 days after treatment
Non-relapse mortality
Treatment Related Mortality (TRM) at 1 year is the percentage of patients who expire from treatment related toxicity attributed to transplant up to 1 year after transplant.
Time frame: 1 year post transplant
Overall Survival
Overall Survival (OS) at 1 year is the percentage of patients alive at 1 year after transplant.
Time frame: 1 year post transplant
Rate of relapse
Relapse incidence at 1 year is the percentage of patients who experience relapse of their hematologic malignancy up to 1 year after transplant.
Time frame: 1 year post transplant
Disease free survival
Disease Free Survival at 1 year is the percentage of patients alive and without evidence of hematologic malignancy at 1 year after transplant.
Time frame: 1 year post transplant
Incidence of chronic GVHD
Chronic graft versus host disease (cGVHD) 1-year cumulative incidence is the percentage of patients who experienced any cGVHD up to 1 year after transplant.
Time frame: 1 year post transplant
Incidence of chronic GVHD
Chronic graft versus host disease (cGVHD) 2-year cumulative incidence is the percentage of patients who experienced any cGVHD up to 2 years after transplant.
Time frame: 2 years post transplant
Incidence of chronic GVHD
Chronic graft versus host disease (cGVHD) 3-year cumulative incidence is the percentage of patients who experienced any cGVHD up to 3 years after transplant.
Time frame: 3 years post transplant
Rate of Grade III-IV aGVHD
Grade III-IV aGVHD prevalence at T+100 is the percentage of patients who have grade III-IV aGVHD at T+100.
Time frame: 100 days after treatment
Rate of Grade II-IV aGVHD
Grade II-IV aGVHD prevenance at T+100 is the percentage of patients who have grade II-IV aGVHD at T+100.
Time frame: 100 days after treatment
Rate of Grade III-IV aGVHD
Grade III-IV aGVHD prevalence at T+180 is the percentage of patients who have grade III-IV aGVHD at T+180.
Time frame: 180 days after treatment
Rate of Grade II-IV aGVHD
Grade II-IV aGVHD prevalence at T+180 is the percentage of patients who have grade II-IV aGVHD at T+180.
Time frame: 180 days after treatment
CMV reactivation rate
The cumulative incidence of CMV reactivation at 1 year is defined as the detection of CMV within any organ by biopsy or within the plasma within the first year of transplant.
Time frame: 1 year after transplant
EBV reactivation rate
The cumulative incidence of EBV reactivation at 1 year is defined as the detection of EBV in the plasma or blood less than 1000 copies/ml within the first year of transplant.
Time frame: 1 year after treatment
Time to neutrophil engraftment
Neutrophil engraftment will be calculated as the days from transplant where the absolute neutrophil count (ANC) reaches \>500cells/ul x 3 days.
Time frame: Within first 30 days of transplant
Time to platelet engraftment
Platelet engraftment will be calculated as the days from transplant where the platelet count reaches 20,000 platelets /ul without the need of transfusion of platelets for 7 days.
Time frame: Within first 60 days of transplant
Donor chimerism
Donor chimerism rates will drawn at day 100 post transplant.
Time frame: Day 100 post transplant
Donor chimerism
Donor chimerism rates will drawn 1 year post transplant.
Time frame: 1 year post transplant
Time to taper off tacrolimus
The average time to taper off of tacrolimus will be calculated.
Time frame: Within 1 year of transplant
Time to taper off MMF
The average time to taper off of mycophenolate mofetil (MMF) will be calculated.
Time frame: Within 90 days of transplant
Assessment of aGVHD biomarker ST2
An assessment of aGVHD biomarker ST2 will occur 7 days post transplant.
Time frame: 7 days post transplant
Assessment of aGVHD biomarker ST2
An assessment of aGVHD biomarker ST2 will occur 28 days post-transplant.
Time frame: 28 days post transplant
Assessment of aGVHD biomarker REG3α
An assessment of aGVHD biomarker REG3α will occur 7 days post-transplant.
Time frame: 7 days post transplant
Assessment of aGVHD biomarker REG3α
An assessment of aGVHD biomarker REG3α will occur 28 days post-transplant.
Time frame: 28 days post transplant
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