Clinical Trial of Upfront Haploidentical or Unrelated Donor BMT to Restore Normal Hematopoiesis in Aplastic Anemia

This study is a prospective, multicenter Phase II study of hematopoietic stem cell transplantation for previously untreated patients with severe aplastic anemia (SAA). Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. Patients with aplastic anemia have low white blood cells (cells which fight infection), low red blood cells (cells that carry oxygen throughout the body), and low platelets (cells that help form clots and prevent bleeding). Treatments for SAA seeks to repair this abnormal immune system attack and allow the bone marrow to make the normal amount of blood cells. This can be done with a bone marrow transplant or with medications to suppress the immune system.

Historically, transplant therapy for SAA has been reserved for patients under 40 years old who had an available fully matched related donor. The standard treatment for older patients with SAA and patients who do not have a fully matched related donor has been treatment using transfusions, medications that suppress the immune system (immunosuppressive therapy, IST), and medications that try to stimulate the bone marrow to produce more cells. For these patients, transplant was used only if a patient did not respond to these interventions. However, progress has made transplantation safer and allowed for half-matched related donor or full or partially-matched unrelated donors to be used with success rates similar to fully matched related donors in many situations. The goals of this study are to determine if patients with SAA who have not received previous treatment for SAA can be treated effectively with transplant as their first SAA therapy.

This is a parallel cohort study comprised of two cohorts based on donor selection: haploidentical related donors and unrelated donors. The accrual goal is 30 participants enrolled and starting protocol-specified conditioning in each cohort, yielding 60 participants in total. Participants will be treated with a reduced-intensity preparative regimen of fludarabine (150 mg/m2), cyclophosphamide (29 mg/kg), low dose total body irradiation (TBI, 400 cGy), and Thymoglobulin® (4.5 mg/kg). Bone marrow will be collected from donors and fresh (not cryopreserved) cells will be given to patients. GVHD prophylaxis will be with post-HSCT cyclophosphamide (100 mg/kg), tacrolimus, and mycophenolate mofetil (MMF). All patients will receive the same conditioning regimen and GVHD prophylaxis. Participants will be followed for 1 year post-transplant.