This early phase I trial tests the effect of abatacept in combination with with two regularly used drugs, mycophenolate mofetil (MMF) and tacrolimus, in preventing graft-versus-host disease (GVHD) in patients receiving omidubicel hematopoietic cell transplant (HCT) for their blood cancer. When healthy stem cells from a donor, such as omidubicel, are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets (and may help destroy any remaining cancer cells). Sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). Abatacept is a immunomodulator drug that works to decrease the body's immune response by blocking the activation of T-cells (immune cells) and may help prevent or reduce the risk of GVHD. Tacrolimus and MMF are in a class of medications called immunosuppressants. They work by decreasing the activity of the immune system to prevent it from attacking the transplant and reduce the risk of rejection. Giving abatacept in combination with standard of care (SOC) drugs, MMF and tacrolimus, after the transplant may be safe, tolerable and/or effective in preventing GVHD following omidubicel HCT.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06731504.
Locations matching your search criteria
United States
North Carolina
Durham
Duke University Medical CenterStatus: Active
Contact: Sanghee Hong
Phone: 919-684-8964
PRIMARY OBJECTIVE:
I. To evaluate safety and feasibility of abatacept as GVHD prophylaxis for omidubicel hematopoietic cell transplantation (HC) as measured by rate of serious adverse events (SAEs).
SECONDARY OBJECTIVES:
I. to assess the efficacy of tacrolimus/MMF/abatacept GVHD prophylaxis after omidubicel transplantation as measured by:
Ia. Acute grade III-IV GVHD-free and relapse-free survival (SRFS);
Ib. Rates of grade II-IV and III-IV acute GVHD per Glucksberg criteria;
Ic. Rates of chronic GVHD-mild, moderate, and severe per National Institute of Health (NIH) criteria;
Id. Hematologic recovery: neutrophil and platelet engraftment at 30 days post-transplant;
Ie. Rates of severe infections and viral reactivations at 6 months post-transplant;
If. Proportion of patients with full or mixed donor chimerism or graft rejection at days 28, 60, and 90 days post-transplant;
Ig. Disease relapse or progression as assessed by bone marrow assessment at 90 days post-transplant;
Ih. Non-relapse mortality (NRM);
Ij. Disease-free survival;
Ik. Overall survival.
EXPLORATORY OBJECTIVES:
I. Will examine the relationship between abatacept day +5 trough level and rates of acute GVHD.
II. Will examine abatacept pharmacokinetic changes (peak and trough levels as well as area under the curve [AUC] calculation) as related to acute and chronic GVHD.
OUTLINE:
Patients receive conditioning therapy with total body irradiation (TBI), fludarabine and thiotepa (TT) or TBI and fludarabine or TT, busulfan and fludarabine or cyclophosphamide IV, fludarabine, TT and TBI prior to transplant. Patients receive omidubicel on day 0, abatacept intravenously (IV) over 30 minutes on days -1, 5, 14 and 28 in the absence of disease progression or unacceptable toxicity. Patients also receive SOC MMF IV or orally (PO) every 8 hours on days 5-60 and tacrolimus IV or PO on days -2 to 90 in the absence of disease progression or unacceptable toxicity. Patients may continue to receive MMF and tacrolimus if active GVHD is present. Additionally, patients undergo chest x-ray or chest computed tomography (CT) at screening and bone marrow aspiration and biopsy and blood sample collection throughout the study.
After completion of study treatment, patients are followed at days 196, 365 and 532 post-transplant.
Lead OrganizationDuke University Medical Center
Principal InvestigatorSanghee Hong
