ABBA CORD: Double Umbilical Cord Blood Transplants With Abatacept for Graft Versus Host Disease Prophylaxis
Summary
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.
Detailed description
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.
Arms & interventions
- DrugCyclophosphamide
Cyclophosphamide (Cy) is one part of the conditioning regimen. 50 mg/kg beginning on day -6.
- DrugFludarabine
Fludarabine (Flu) is one part of the conditioning regimen. 150 mg/m2 (30 mg/m2 per day on days -6 to -2)
- DrugThiotepa
Thiotepa (Thio) is one part of the conditioning regimen.10 mg/kg (5 mg/kg per day on days -5 and -4)
- RadiationTotal Body Irradiation
400 cGy (200 cGy per day on days -2 and -1).
- BiologicalDouble Umbilical Cord Transplant
Cord blood is a regulated biologic. Selection of cord blood units will be based on published guidelines.
- DrugTacrolimus
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.
- DrugMycophenolate Mofetil
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.
- DrugAbatacept
Abatacept at a dose of 10mg/kg will be given on days T-1, T+5, T+14 and T+28.
Outcome measures
Primary
Severe aGVHD free survival
To assess severe aGVHD (grade III-IV acute GVHD) free survival (SGFS) at T+180.
Time frame: 180 days after treatment
Secondary
Non-relapse mortality
Time frame: 1 year post transplant
Overall Survival
Time frame: 1 year post transplant
Rate of relapse
Time frame: 1 year post transplant
Disease free survival
Time frame: 1 year post transplant
Incidence of chronic GVHD
Time frame: 1 year post transplant
Incidence of chronic GVHD
Time frame: 2 years post transplant
Incidence of chronic GVHD
Time frame: 3 years post transplant
Rate of Grade III-IV aGVHD
Time frame: 100 days after treatment
Rate of Grade II-IV aGVHD
Time frame: 100 days after treatment
Rate of Grade III-IV aGVHD
Time frame: 180 days after treatment
Rate of Grade II-IV aGVHD
Time frame: 180 days after treatment
CMV reactivation rate
Time frame: 1 year after transplant
EBV reactivation rate
Time frame: 1 year after treatment
Time to neutrophil engraftment
Time frame: Within first 30 days of transplant
Time to platelet engraftment
Time frame: Within first 60 days of transplant
Donor chimerism
Time frame: Day 100 post transplant
Donor chimerism
Time frame: 1 year post transplant
Time to taper off tacrolimus
Time frame: Within 1 year of transplant
Time to taper off MMF
Time frame: Within 90 days of transplant
Assessment of aGVHD biomarker ST2
Time frame: 7 days post transplant
Assessment of aGVHD biomarker ST2
Time frame: 28 days post transplant
Assessment of aGVHD biomarker REG3α
Time frame: 7 days post transplant
Assessment of aGVHD biomarker REG3α
Time frame: 28 days post transplant
Eligibility criteria
Study locations (1)
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106