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

Summary

Objectives

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.