The phase 2, OPTIMIZE study is set to investigate the effectiveness of reduced dose, post-transplantation cyclophosphamide (PTCy) therapy for the prevention of graft-versus-host disease in patients with hematologic malignancies, including myelodysplastic syndromes (MDS), after receiving an HLA-mismatched unrelated donor transplantation.
The study, sponsored by the Center for International Blood and Marrow Transplant Research, is not recruiting yet.
The researchers will analyze the ability of a reduced dose of PTCy to prevent the occurrence of infections during the first 100 days after transplantation as well as its ability to prevent graft-versus-host disease as effectively as the standard dose treatment.
The study will enroll approximately 170 adult patients with MDS according to complex inclusion criteria. The participants will be divided into 5 groups and given different treatments.
Read more about MDS therapies
All participants will receive a peripheral blood stem cell graft infusion from a mismatched unrelated donor on day 0, followed by a reduced dose of cyclophosphamide (25 mg/kg per dose) on days 3 and 4 post-transplant.
The first group of patients will receive additional intravenous or oral busulfan (≥9 mg/kg total dose) on days −6 to −3 as well as intravenous fludarabine (150 mg/m2 total dose) on days −6 to −2 (regimen A). The second group will receive intravenous fludarabine (90 mg/m2 total dose) on days −7 to −5 as well as total body irradiation (1200 cGy total dose) on days −4 to −1 (regimen B).
The third group will receive intravenous fludarabine (150-180 mg/m2 total dose) on days −6 to −2 and busulfan (≤8 mg/kg administered orally or 6.4 mg/kg administered intravenously) on days −5 and −4 (regimen C), while the fourth group will receive intravenous fludarabine (125-150 mg/m2 total dose) on days −7 to −3 and intravenous melphalan (100-140 mg/m2) on day −1 (regimen D).
The fifth group will receive intravenous fludarabine (150 mg/m2 total dose) on days −6 to −2, intravenous cyclophosphamide (29-50 mg/kg) on days −6 and −5, as well as total body irradiation (200 cGy) on day −1 (regimen E).
Read more about MDS prognosis
The researchers will analyze survival at 100 days without grade 2 to 3 infections as the primary outcome measure.
The secondary outcome measures will include overall survival, overall toxicity, progression-free survival, infection-free survival, graft-versus-host-disease relapse-free survival, nonrelapse mortality, donor T-cell chimerism, incidence and severity of cytokine release syndrome, as well as cumulative incidences of neutrophil recovery, platelet recovery, primary and secondary graft failure, acute and chronic graft-versus-host disease, grade 2 to 3 bacterial, fungal, and viral infections, grade 2 to 3 BK virus hemorrhagic cystitis, and relapse/progression.
The study is set to start on November 1, 2023, with estimated completion date set for June 30, 2026.
Reference
HLA-mismatched unrelated donor peripheral blood stem cell transplantation with reduced dose post transplantation cyclophosphamide GvHD prophylaxis (OPTIMIZE). ClinicalTrials.gov. Last updated August 21, 2023. Accessed August 31, 2023.
