This phase II trial tests how well hematopoietic cell transplant with individualized, reduced intensity conditioning and post-transplant cyclophosphamide works in treating patients with severe aplastic anemia and other forms of acquired bone marrow failure. Giving chemotherapy, with rituximab, rabbit anti-thymocyte globulin (ATG), cyclophosphamide, fludarabine and total-body irradiation before a hematopoietic stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor 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 graft-versus-host disease). Giving cyclophosphamide shortly after the transplant may stop this from happening. Giving hematopoietic cell transplant with individualized, reduced intensity conditioning and post-transplant cyclophosphamide may be effective in treating patients with severe aplastic anemia and other forms of acquired bone marrow failure.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06412497.
Locations matching your search criteria
United States
Minnesota
Minneapolis
University of Minnesota/Masonic Cancer CenterStatus: Active
Contact: Christen Layne Ebens
Phone: 612-626-8094
PRIMARY OBJECTIVE:
I. To determine the grade 3-4 acute graft-versus host disease (GvHD), chronic GvHD-free, failure-free survival (GFFS) at 1-year post-HCT.
SECONDARY OBJECTIVES:
I. To determine the grade 3-4 acute GvHD, chronic GvHD-free, failure-free survival (GFFS) at 2 years post hematopoietic cell transplant (HCT).
II. To determine the incidence of neutrophil recovery at day 42 post HCT.
III. To determine the incidence of platelet recovery at 6 months post HCT.
IV. To determine the incidence of grade 3-4 acute GvHD at 100 days post HCT.
V. To determine the incidence of any chronic GvHD at 1 year post HCT.
VI. To determine the incidence of primary graft failure at day +42.
VII. To determine the incidence of secondary graft failure at 1 year.
VIII. To determine the incidence of non-relapse mortality at 100 days and 1 year.
IX. To determine the overall survival at 1 and 2 years.
X. To determine the incidence of pre-malignant clonal hematopoiesis recurrence at 1 and 2 years (Arm B with baseline clonal hematopoiesis only).
XI. To determine the incidence of EBV reactivation requiring pre-emptive therapy by day +180 amongst patients receiving day -14 rituximab (EBV IgG seropositive or EBV blood PCR positive).
CORRELATIVE OBJECTIVES:
I. Immune recovery at days +60, +100, 6 months, 1 and 2 years post-HCT.
II. Peripheral blood donor myeloid, lymphoid, B and NK cell chimerism at days +28, +60, +100, 6 months, 1 and 2 years post-HCT.
III. Incidence of major bacterial, viral, and fungal infections by day+180.
OUTLINE: Patients less than or equal to 25 years old with no clonal hematopoiesis are assigned to Arm A and patients greater than 25 and/or with clonal hematopoiesis are assigned to Arm B.
ARM A: Patients who are positive for current or prior Epstein-Barr virus (EBV) receive rituximab intravenously (IV) once on day -14. Patients receive rabbit anti-thymocyte globulin (ATG) over 4-6 hours once per day (QD) on days -9 to -7, cyclophosphamide IV over 2 hours QD on days -6 to -5, fludarabine IV QD on days -6 to -3 and total body irradiation once on day -1. Patients then receive hematopoietic stem cells IV on day 0. Patients receive cyclophosphamide IV over 2 hours QD on days +3 and +4. Patients undergo computed tomography (CT) during screening and echocardiography (ECHO), bone marrow biopsy and aspiration throughout the trial.
ARM B: Patients who are positive for current or prior EBV receive rituximab IV once on day -14. Patients receive rabbit ATG over 4-6 hours QD on days -9 to -7, cyclophosphamide IV over 2 hours QD on day -6 to -5, fludarabine IV QD on days -6 to -3 and total body irradiation twice on day -1. Patients then receive hematopoietic stem cells IV on day 0. Patients receive cyclophosphamide IV over 2 hours QD on days +3 and +4. Patients undergo CT during screening and ECHO, bone marrow biopsy and aspiration throughout the trial.
After completion of study treatment, patients are followed up weekly until day +100, at +101 to +179, 6 months, 1 and 2 years.
Lead OrganizationUniversity of Minnesota/Masonic Cancer Center
Principal InvestigatorChristen Layne Ebens
