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

Overview

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.

Interventions

• Drug Abatacept
  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.

Primary outcome measures

• Safety of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as evaluated by frequency of adverse events. [Time frame: 6 months post-HCT]
• Safety of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as evaluated by severity of adverse events. [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. [Time frame: Day 28 post-HCT]

Secondary outcome measures (11)

• Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by Severe GVHD-Free and Progression-Free Survival (SRFS). [Time frame: 18 months post-HCT]
• Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by rates of acute GVHD. [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. [Time frame: 18 months post-HCT]
• Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by hematologic recovery. [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. [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. [Time frame: 6 months post-HCT]
• Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by donor cell engraftment. [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. [Time frame: Day 90 post-HCT]
• Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by non-relapse mortality (NRM). [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). [Time frame: 18 months post-HCT]
• Efficacy of ABA/Tac/MMF GVHD prophylaxis following omidubicel HCT as measured by overall survival (OS). [Time frame: 18 months post-HCT]

Eligibility criteria

Inclusion criteria

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

• Left ventricular ejection fraction ≥ 40%;
• DLCO, FEV1, FVC > 50% predicted;
• 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);
• Serum creatinine within normal range, or if serum creatinine outside normal range, must have measured or estimated creatinine clearance > 40 mL/min/1.73m2;
• Karnofsky performance score ≥ 70; and
• If applicable, > 6 months since a previous autologous transplant.
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• Duke University Health System — Durham

Identifiers

NCT: NCT06731504 · Pro00116015

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗