This study is a single-center, non-randomized, single-arm pilot trial of omidubicel hematopoietic stem cell transplantation (HCT) for hematologic malignancies with myeloablative conditioning chemotherapy of physician's choice followed by abatacept/tacrolimus/mycophenolate mofetil (ABA/Tac/MMF) graft-versus-host disease (GVHD) prophylaxis. The primary objective is to assess the safety and feasibility of abatacept/tacrolimus/mycophenolate mofetil GVHD prophylaxis following omidubicel HCT. Target enrollment is 10 participants. Subjects are adults with a diagnosis of hematologic malignancy with an available cord blood unit for omidubicel product manufacturing. Patients will be followed for a total of 18 months and will have research blood draws and Abatacept pharmacokinetics, as well as standard of care assessments that will be reviewed for this study. It is estimated that 36 months of accrual will be necessary to enroll the targeted sample size with an accrual rate of approximately 1 participant every 3 months. Accrual will be reported by race, ethnicity, gender, and age. Descriptive analyses are planned given the sample size.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
10
Abatacept is a monoclonal antibody that suppresses T-cell activation through costimulatory blockade. In 2021, abatacept was FDA approved to prevent acute GVHD following allogeneic HCT.
Duke University Health System
Durham, North Carolina, United States
RECRUITINGSafety of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as evaluated by frequency of adverse events.
Adverse events are defined by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Only events related to Abatacept (and not solely expected toxicities of omidubicel HCT) will be recorded.
Time frame: 6 months post-HCT
Safety of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as evaluated by severity of adverse events.
Adverse events are defined by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Only events related to Abatacept (and not solely expected toxicities of omidubicel HCT) will be recorded.
Time frame: 6 months post-HCT
Feasibility of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as evaluated by number of subjects who receive minimum dose of ABA.
Minimum dose is 4 doses of minimum 10mg/kg of abatacept prophylaxis following omidubicel transplant.
Time frame: Day 28 post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by Severe GVHD-Free and Progression-Free Survival (SRFS).
Severe GVHD-Free and Progression-Free Survival (SRFS) as a time to event outcome is defined as the first event of Grade III-IV acute GVHD or chronic GVHD requiring systemic immune suppression, with underlying disease progression or relapse, and death by any cause.
Time frame: 18 months post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of acute GVHD.
Cumulative incidences of Grade II-IV and III-IV acute GVHD will be determined per Glucksberg criteria.
Time frame: 18 months post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of chronic GVHD - mild, moderate, and severe per NIH criteria.
The cumulative incidence of chronic GVHD will be determined per NIH Consensus Conference Criteria.
Time frame: 18 months post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by hematologic recovery.
Hematologic recovery is defined by achieving both neutrophil and platelet count recovery after transplant. Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm3 for three consecutive measurements on three different days. Platelet recovery is defined as the first day of a sustained platelet count (1) greater than or equal to 20,000/mm3 or (2) greater than or equal to 50,000/mm3 with no platelet transfusions in the preceding seven days.
Time frame: 30 days post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of severe infections at 6 months post-transplant.
The incidence of definite and probable viral, fungal, and bacterial infections will be tabulated.
Time frame: 6 months post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of viral reactivations at 6 months post-transplant.
The cumulative incidence of treated CMV and HHV6 reactivation in the first 6 months post-transplant will be described.
Time frame: 6 months post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by donor cell engraftment.
Donor cell engraftment will be assessed by donor/recipient chimerism studies. Chimerism may be evaluated in bone marrow, whole unfractionated blood, or blood cell fractions, including CD3 and CD33 or CD15 fraction.
Time frame: Day 28, 60, and 90 post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by disease relapse or progression.
Relapse or progression will be diagnosed by bone marrow assessment.
Time frame: Day 90 post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by non-relapse mortality (NRM).
NRM is defined as death without evidence of disease progression or recurrence.
Time frame: Day 100, 180, and 365 post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by disease-free survival (DFS).
DFS is defined as the time from date of transplant to death or relapse/progression, whichever comes first.
Time frame: 18 months post-HCT
Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by overall survival (OS).
OS is defined as the time interval between date of transplant and death from any cause.
Time frame: 18 months post-HCT
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