Immunosuppressive Therapy versus
Unrelated Donor Transplant
TransIT
A phase III randomized trial comparing unrelated donor bone marrow transplantation with immune suppression therapy for newly diagnosed pediatric and young adult patients with severe aplastic anemia.
ABOUT
What is aplastic anemia?
Aplastic anemia is a bone marrow condition. Bone marrow is a tissue inside the bones. With aplastic anemia, the bone marrow does not make enough red blood cells to carry oxygen, white blood cells to fight infection, or platelets to control bleeding.
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Severe aplastic anemia (SAA) can be treated with immune suppressive therapy (IST) or a bone marrow transplant (BMT). Current treatment for patients with aplastic anemia who have a matched sibling (brother or sister), or family donor is a bone marrow transplant. Patients without a matched family donor are currently treated in most centers in the United States with IST.
Study Purpose
The TransIT study is a Phase III randomized trial comparing unrelated donor BMT with IST as an initial therapy for newly diagnosed pediatric and young adult patients with SAA.
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​Currently, the standard of care for SAA in children and young adults mimics that in adults up to age 40. In the absence of a matched related donor for BMT, this includes IST. With improved matched-unrelated-donor (MUD) BMT outcomes over the past decade, there is now a question as to the best up-front treatment for this disease, but there have been no randomized trials to determine whether the standard of care for children and young adults with SAA should be changed. The field is currently in a state of uncertainty regarding the most effective form of upfront treatment — IST vs. MUD BMT — and this trial will help define the best initial approach.
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Study Details
The study will randomize 234 children or young adults over 2 years at a 1:1 ratio between initial treatment with IST with hATG/cyclosporine (CsA) versus well-matched (9-10/10 allele) MUD BMT using a regimen of rATG/fludarabine/ cyclophosphamide and 200cGy TBI.
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The primary endpoint will be failure free survival of IST versus BMT.
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Secondary endpoints include proportion of subjects with failure of IST or BMT before or at 2 years, proportion of subjects with inadequate counts at 2 years, proportion of subjects on systemic immune suppression at 2 years, time from randomization to initiation of IST or BMT, frequency and reasons for failure to receive randomized therapy, rates of bloodstream infection, time to T- and B-cell immune reconstitution in the URD BMT arm and IgG levels free of IVIG replacement, proportion of subjects who have died from treatment or other reasons, time from randomization to response, time from initiation of therapy to response, proportion of subjects with engraftment, severe acute and chronic GVHD, and graft failure in the BMT arm, rates of IST response and failure, secondary therapies given for failure of primary randomized therapy and the level of response, rates of subsequent neoplasms or PNH clone in both arms, HR-QoL as reported by patients in both arms, and comparison of markers of gonadal function in both arms.
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Biology aims include assessment of germline genetic causes of pediatric aplastic anemia, assessment of clonal hematopoiesis in SAA following IST vs BMT, and comparison of immune suppression free survival with adequate counts at two years between the two arms.
ELIGIBILITY
Who can participate?
Inclusion Criteria
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Confirmed diagnosis of idiopathic SAA.
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Age ≤25 years old.
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No suitable fully matched related donor available.
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At least 2 unrelated donors noted on NMDP search who are well matched.
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Signed informed consent for the randomized trial by patient and/or legal guardian.
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No obvious contradictions to BMT or IST.
Exclusion Criteria
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Inherited bone marrow failure syndromes.
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Clonal cytogenetic abnormalities or fluorescence In Situ Hybidization (FISH) pattern consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.
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Known severe allergy to horse ATG.
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Prior allogeneic or autologous stem cell transplant.
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Prior solid organ transplant.
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Infection with human immunodeficiency virus (HIV).
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Active Hepatitis B or C.
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Female patients who are pregnant or breast-feeding.
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Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.
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Disease modifying treatment prior to study enrollment, including but not limited to use of androgens, eltrombopag, romiplastin, or immune suppression. Note: Supportive care measures such as G-CSF, blood transfusion support and antibiotics are allowable.
TransIT Study Overview
with Dr. David Williams and Dr. Michael Pulsipher
LEADERSHIP
Principal Investigators
David A. Williams, MD
Boston Children's Hospital
david.williams2@childrens.harvard.edu
Staci Arnold, MD, MBA, MPH
Children's Hospital of Atlanta
staci.denise.arnold@emory.edu
Michael A. Pulsipher, MD
University of Utah
michael.pulsipher@hci.utah.edu
Co-Investigators
Akiko Shimamura, MD PhD
Boston Children's Hospital
akiko.shimamura@childrens.harvard.edu
Edie Weller, PhD
Boston Children's Hospital
edie.weller@childrens.harvard.edu
Bronwen Shaw, MD
Center for International Blood &
Marrow Transplant Research
Medical College of Wisconsin
beshaw@mcw.edu
Data Coordinating Center
Center for International Blood & Marrow Transplant Research
Medical College of Wisconsin
Clinical Project Manager: Kristi Wilmes, MS, CCRP
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Clinical Coordinating Center
Boston Children's Hospital
Project Manager: Maggie Malsch, MSN, RN, CPHON
TransITsamples-dl@childrens.harvard.edu
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SPONSORS
Sponsored by the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) in partnership with the Center for International Blood and Marrow Transplant Research (CIBMTR).
