Clinical trial NCT06731504: HMCT/CT2401: Abatacept GVHD Prophylaxis Following Omidubicel HCT
Official title: A Pilot Trial of Abatacept Based Graft-Versus-Host Disease Prophylaxis Following Omidubicel Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Hematologic Malignancy
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2024-12-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. A diagnosis of hematologic malignancy with an available cord blood unit for omidubicel product manufacturing
2. Adult patients (≥18 at the time of enrollment)
3. Adequate organ function for transplant defined as:

   1. Left ventricular ejection fraction ≥ 40%;
   2. DLCO, FEV1, FVC \> 50% predicted;
   3. Total bilirubin ≤ 2.5 mg/dL except for patients with Gilbert's syndrome or hemolysis, and ALT, AST, and alkaline phosphatase all \< 5 x upper limit of normal (ULN);
   4. Serum creatinine within normal range, or if serum creatinine outside normal range, must have measured or estimated creatinine clearance \> 40 mL/min/1.73m2;
   5. Karnofsky performance score ≥ 70; and
   6. If applicable, \> 6 months since a previous autologous transplant.
4. Female patients (unless postmenopausal or surgically sterilized) and male patients (even if surgically sterilized) must agree to practice two effective methods of contraception at the same time, or agree to completely abstain from heterosexual intercourse from the time of signing informed consent through 100 days post-transplant. Fertility preservation method will be left to treating physician's discretion.

Exclusion Criteria:

1. Patients with known sensitivity to dimethyl sulfoxide, dextran 40, gentamicin, human serum albumin or bovine material
2. Presence of a donor-specific antibodies with MFI \>2000
3. Uncontrolled bacterial, fungal or viral infection
4. Treatment with any other investigational medical product (medications without any known FDA approved indication) needs to be discussed with the PI for patient eligibility.

Primary outcomes:
measure: Safety of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as evaluated by frequency of adverse events.
timeFrame: 6 months post-HCT
measure: Safety of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as evaluated by severity of adverse events.
timeFrame: 6 months post-HCT
measure: Feasibility of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as evaluated by number of subjects who receive minimum dose of ABA.
timeFrame: Day 28 post-HCT
Secondary outcomes:
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by Severe GVHD-Free and Progression-Free Survival (SRFS).
timeFrame: 18 months post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of acute GVHD.
timeFrame: 18 months post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of chronic GVHD - mild, moderate, and severe per NIH criteria.
timeFrame: 18 months post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by hematologic recovery.
timeFrame: 30 days post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of severe infections at 6 months post-transplant.
timeFrame: 6 months post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of viral reactivations at 6 months post-transplant.
timeFrame: 6 months post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by donor cell engraftment.
timeFrame: Day 28, 60, and 90 post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by disease relapse or progression.
timeFrame: Day 90 post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by non-relapse mortality (NRM).
timeFrame: Day 100, 180, and 365 post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by disease-free survival (DFS).
timeFrame: 18 months post-HCT
measure: Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by overall survival (OS).
timeFrame: 18 months post-HCT
Other outcomes:
Locations:
Study officials:
affiliation: Duke Health
name: Sanghee Hong, MD
role: PRINCIPAL_INVESTIGATOR
References: