Severe Aplastic AnemiaPhase 3TransITNCT05600426
A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)
A Phase 3 study testing cyclosporine, Matched Unrelated Donor Hematopoetic Stem Cell Transplant and horse anti-thymocyte globulin (ATG) in people with Severe Aplastic Anemia, run by Boston Children's Hospital at 52 sites in 2 countries.
Trial summary
Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant. Read more about this study
- Who is it for?
- Ages 0 to 25 years
- Conditions the study is for
- Severe Aplastic Anemia
- What is being tested?
- cyclosporine, Matched Unrelated Donor Hematopoetic Stem Cell Transplant and horse anti-thymocyte globulin (ATG)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 52 sitesin 2 countries
- Study dates
- 25 Jan 2023to 6 Aug 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- To be eligible to participate in the randomized trial, an individual must meet all the following criteria:
- Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian.
- Age ≤25 years old at time of randomized trial consent.
- Confirmed diagnosis of idiopathic SAA, defined as:
- Bone marrow cellularity <25%, or <30% hematopoietic cells.
- Two of three of the following (in peripheral blood): neutrophils <0.5 x 10^9/L, platelets <20 x 10^9/L, absolute reticulocyte count <60 x 10^9/L or hemoglobin <8 g/dL.
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- No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing).
- At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution).
- In the treating physician's opinion, no obvious contraindications precluding them from BMT or IST.
Who cannot join
- Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic isoamylase testing is not useful in children <3). Other testing per center may be performed to exclude IBMFS.
- Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.
- Known severe allergy to ATG.
- Prior allogeneic or autologous stem cell transplant.
- Prior solid organ transplant.
- Infection with human immunodeficiency virus (HIV).
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- Active Hepatitis B or C. This only needs to be excluded in patients where there is clinical suspicion of hepatitis (e.g., elevated LFTs).
- Female patients who are pregnant or breast-feeding.
- Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.
- Disease modifying treatment prior to study enrollment, including but not limited to use of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportive care measures such as G-CSF, blood transfusion support and antibiotics are allowable
Trial locations and contacts
52 sites in 2 countries.
52 sites in 2 countries
United States50 sites
University of Michigan
Ann Arbor, Michigan, 48109
Children's Hospital of Atlanta/Emory
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Boston Children's Hospital
Boston, Massachusetts, 02115
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
University of North Carolina
Chapel Hill, North Carolina, 27599
Levine Children's Hospital
Charlotte, North Carolina, 28203
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Medical Center Dallas
Dallas, Texas, 75235
Duke University
Durham, North Carolina, 27705
University of Florida
Gainesville, Florida, 32610
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Texas Children's Hospital
Houston, Texas, 77030
Indiana University Hospital/Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Arkansas
Little Rock, Arkansas, 72202
Loma Linda
Loma Linda, California, 92354
Children's Hospital Los Angeles
Los Angeles, California, 90027
UCLA
Los Angeles, California, 90095
University of Wisconsin
Madison, Wisconsin, 53792
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Miami
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
Vanderbilt University Medical Center
Nashville, Tennessee, 37203
Yale University
New Haven, Connecticut, 06520
Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Children's Hospital NOLA
New Orleans, Louisiana, 70118
Columbia University Medical Center
New York, New York, 10032
Children's Hospital of the King's Daughter
Norfolk, Virginia, 23507
Children's Hospital & Research Center Oakland
Oakland, California, 94609
Children's Hospital of Orange County
Orange, California, 92868
Stanford
Palo Alto, California, 94304
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Oregon Health & Science University
Portland, Oregon, 97239
Mayo Clinic Rochestser
Rochester, Minnesota, 55902
University of Utah/Primary Children's Hospital
Salt Lake City, Utah, 84112
Methodist Healthcare
San Antonio, Texas, 78229
Rady Children's Hospital San Diego
San Diego, California, 92123
University of California San Francisco
San Francisco, California, 94158
Maine Health
Scarborough, Maine, 04074
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Washington University in St. Louis
St Louis, Missouri, 63110
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Children's National Hospital
Washington D.C., District of Columbia, 20010
Nemours Children's Hospital, Delaware
Wilmington, Delaware, 19803
Canada2 sites
British Columbia Children's
Vancouver, British Columbia, V6H 3V4
Winnipeg CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
About this study
Official title: A Phase III Randomized Trial Comparing Unrelated Donor Bone Marrow Transplantation With Immune Suppressive Therapy for Newly Diagnosed Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)
Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant. Regular 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 normally are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bone marrow transplant (BMT) is used as a secondary treatment in patients who did not get better with IST, had their disease come back, or a new worse disease replaced it (like leukemia).
This trial will compare time from randomization to failure of treatment or death from any cause of IST versus URD BMT when used as initial therapy to treat SAA.
Read more
The trial will also assess whether health-related quality of life and early markers of fertility differ between those randomized to URD BMT or IST, as well as assess the presence of marrow failure-related genes and presence of gene mutations associated with MDS or leukemia and the change in gene signatures after treatment in both study arms.
This study treatment does not include any investigational drugs. The medicines and procedures in this study are standard for treatment of SAA.
Read the detailed description
This study is a multi-center randomized phase III trial to compare the failure free survival between those randomized to IST vs 9-10/10 HLA matched URD BMT. The study will also address patient-reported outcomes and gonadal function in each arm and explore critical biological correlates including assessing germline genetic mutations associated with pediatric SAA that may lead to a predisposition to the disease and the risk of development of clonal hematopoiesis following IST vs BMT in pediatric and young adult SAA.
This clinical trial will randomize 234 children/AYA over 3.3-4.7 years at a 1:1 ratio between initial treatment with immune suppression therapy (IST) with horse ATG (hATG)/cyclosporine (CsA) versus well- matched (9-10/10 allele) unrelated donor (URD) bone marrow transplantation (BMT) using a regimen of rabbit ATG (rATG)/fludarabine/cyclophosphamide and 200 cGy TBI. Duration of subject participation for all study procedures in this study will be up to 2 years after treatment; a single later timepoint between 3 and 5 years will be collected to follow patients for specific protocol defined late effects and survival.
- Conditions
- Severe Aplastic Anemia
- Being tested
- cyclosporine, Matched Unrelated Donor Hematopoetic Stem Cell Transplant, horse anti-thymocyte globulin (ATG), rabbit anti-thymocyte globulin (ATG), Methotrexate
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclosporineDrug
cyclosporine
Matched Unrelated Donor Hematopoetic Stem Cell TransplantProcedure or surgery
Matched Unrelated Donor (MUD) Hematopoietic Stem Cell Transplantation (HSCT)
horse anti-thymocyte globulin (ATG)Drug
Also called ATGAM
horse anti-thymocyte globulin (ATG)
rabbit anti-thymocyte globulin (ATG)Drug
Also called thymoglobulin
rabbit anti-thymocyte globulin (ATG)
MethotrexateDrug
methotrexate
FludarabineDrug
fludarabine
CyclophosphamideDrug
cyclophosphamide
low-dose total body irradiation (TBI)Radiation
low-dose total body irradiation (TBI)
Immunosuppressive Therapy (IST)Procedure or surgery
Immunosuppressive Therapy (IST)
| Study group | Role | What they receive |
|---|---|---|
| Immunosuppressive Therapy | Active comparator | Patient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine. Receives: Drug: cyclosporine; Drug: horse anti-thymocyte globulin (ATG); Procedure: Immunosuppressive Therapy (IST) |
| Matched Unrelated Stem Cell Transplant | Active comparator | Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention. Receives: Drug: cyclosporine; Procedure: Matched Unrelated Donor Hematopoetic Stem Cell Transplant; Drug: rabbit anti-thymocyte globulin (ATG); Drug: Methotrexate; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: low-dose total body irradiation (TBI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint of this trial is time from randomization to treatment failure or death from any cause.
The median time to failure or death will be compared on the two arms using the log-rank test. Failure of IST is defined as the date that a second definitive therapy was recommended (BMT, second course of ATG) and failure of BMT defined as the date that a second definitive therapy was recommended (second BMT, course of ATG).
Measured: Randomization to 2 years post-randomization
Secondary outcomes (27)
Comparison of subjects with failure of IST or BMT before or at 2 years
The proportion of subjects with failure of IST or BMT before or at 2 years. Failure of IST is defined as initiation of a second definitive therapy (BMT, second course of ATG) and failure of BMT defined as initiation of a second definitive therapy (second BMT, course of ATG).
Measured: Randomization to 2 years post-randomization
Comparison of subjects with inadequate counts at 2 years among those who have not died or failed treatment.
The proportion of subjects with inadequate counts at 2 years among those who have not failed therapy or died. Adequate counts are defined as: Absolute Neutrophil Count (ANC) >1 x 10^9/L, Hemoglobin >10g/dL, and Platelets >50 x10^9/L.
Measured: Randomization to 2 years post-randomization
Comparison of subjects on immune suppression therapy at 2 years among those who have not died or failed treatment.
The proportion of subjects on immune suppression therapy at 2 years among those who have not failed therapy or died. Immune suppression is defined as systemic therapies necessary to treat SAA or GVHD (cyclosporine, tacrolimus, etc.). Isolated treatment with topical agents will not be considered as immune suppression therapy.
Measured: Randomization to 2 years post-randomization
Estimate the time from randomization to initiation of IST or BMT.
The median time in days from randomization to initiation of IST or BMT will be estimated. Initiation of therapy is first day of ATG for IST subjects, or day 0 (infusion day) for bone marrow transplant subjects.
Measured: Randomization through Day 100
Comparison of the frequency of failure to receive primary assigned therapy (IST or BMT) and reasons for the failure.
The proportion of subjects who fail to receive randomized therapy and the frequency of reasons for failure.
Measured: Randomization through Day 100
Comparison of the incidence of bacteremia, viremia, and invasive fungal infection in the first two years after randomization in the IST and BMT arms.
Proportion of subjects from the time of randomization in the first 2 years with each of the following:
- Documented bacteremia
- Documented viremia
- Documented invasive fungal infection (defined as confirmed or suspected fungal infection based upon imaging)
Measured: Randomization through two years post randomization
Estimate the median time to T- and B-cell immune reconstitution the first year for the URD BMT Arm
Absolute CD3, CD4, CD8, CD19, and CD56 (NK cell) numbers will be tracked at 100 days, 180 days, 1 year and 2 years post initiation of therapy in URT BMT arm. IgG levels free of IVIG replacement will be collected at the same timepoints. The median time to T- and B-cell reconstitution will be estimated.
Measured: Initiation of therapy (Day 0) to 100 days, 180 days, 1 year and 2 years
Comparison of overall survival at 1 and 2 years from randomization in both arms.
Proportion of subjects who have died at 1 year and 2 years after randomization for any reason.
Measured: Randomization to one year, randomization to two years
Comparison of treatment-related mortality (TRM) at 1 and 2 years from randomization in both arms.
Proportion of subjects who have died at 1 year and 2 years after randomization due to treatment-related reasons. TRM is defined as death in recipients without relapse or progression of their disease. Non-medical, accidental causes of death, e.g., natural disasters, are not considered TRM.
Measured: Randomization to 1 year, randomization to 2 years
Comparison of the median time from randomization to and rates of neutrophil recovery on both arms
The time from randomization to neutrophil recovery. Neutrophil recovery is defined as ANC 0.5 x109/L for 3 consecutive measures for neutrophils (recovery date is the first date).
Measured: Randomization to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from randomization to and rate of platelet recovery on both arms
The time from randomization to platelet recovery. Platelet recovery is defined as platelet levels >= 20 x10^9/L for 3 consecutive measures (recovery is the first date) with no platelet transfusions for 1 full week.
Measured: Randomization to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from randomization to and rates of red blood cell recovery on both arms
The time from randomization to red blood cell recovery. Red blood cell recovery is defined as RBC hemoglobin level >= 8g/dL and 10g/dL with no RBC transfusions for 4 weeks.
Measured: Randomization to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from initiation of therapy to and rates of neutrophil recovery on both arms
The time from initiation of therapy (defined as Day 1 for patients randomized to IST and Day 0 for patients randomized to URD BMT) to neutrophil recovery. Neutrophil recovery is defined as ANC 0.5 x109/L for 3 consecutive measures for neutrophils (recovery date is the first date).
Measured: Initiation of therapy to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from initiation of therapy to and rate of platelet recovery on both arms
The time from initiation of therapy (defined as Day 1 for patients randomized to IST and Day 0 for patients randomized to URD BMT) to platelet recovery. Platelet recovery is defined as platelet levels >= 20 x10^9/L for 3 consecutive measures (recovery is the first date) with no platelet transfusions for 1 full week.
Measured: Initiation of therapy to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from initiation of therapy to and rates of red blood cell recovery on both arms.
The time from initiation of therapy (defined as Day 1 for patients randomized to IST and Day 0 for patients randomized to URD BMT) to red blood cell recovery. Red blood cell recovery is defined as RBC hemoglobin level >= 8g/dL and 10g/dL with no RBC transfusions for 4 weeks.
Measured: Randomization to 100 days, 180 days, 1 year and 2 years
Estimate the rates of engraftment in patients who are randomized to URD BMT.
Proportion of subjects with engraftment in patients who receive URD BMT.
Measured: Randomization to 3-5 years
Estimate the rates of primary graft failure in patients who are randomized to URD BMT .
Proportion of subjects with primary graft failure in patients who receive URD BMT. Primary graft failure is defined as failure to achieve neutrophil recovery by Day +28 following a conditioning regimen induced neutrophil nadir < 0.5 x10^9/L.
Measured: Randomization to 3-5 years
Estimate the rates of secondary graft failure in patients who are randomized to URD BMT .
Proportion of subjects with secondary graft failure in patients who receive URD BMT. Secondary graft failure will be defined as a fall in the neutrophil count after documented primary engraftment to < 0.5 x10^9/L sustained for more than three days that cannot be attributed to other causes such as drugs, infection, GVHD, etc., and is not responsive to G-CSF or GM-CSF.
Measured: Randomization to 3-5 years
Estimate the rates of grade II-IV acute GVHD in patients who are randomized to URD BMT .
Proportion of subjects with grade II-IV in patients who receive URD BMT.
Measured: Randomization to 3-5 years
Estimate the rates of grade III-IV acute GVHD in patients who are randomized to URD BMT.
Proportion of subjects with grade III-IV acute GVHD in patients who receive URD BMT.
Measured: Randomization to 3-5 years
Estimate the rates of severe chronic GVHD in patients who are randomized to URD BMT.
Proportion of subjects with severe chronic GVHD in patients who receive URD BMT.
Measured: Randomization to 3-5 years
Estimate the rates of response of patients randomized to IST
Proportion of subjects with IST response. IST response criteria is:
Complete Response: Hemoglobin ≥10 g/dL and ANC ≥1x10^9/L and Platelets ≥100x10^9/L Very Good Partial Response: Hemoglobin ≥8 g/dL and ANC ≥0.5x10^9/L and Platelets ≥50x10^9/L Partial Response: Hemoglobin ≥8 g/dL and ANC ≥0.5x10^9/L and Platelets ≥20x10^9/L and transfusion independent No Response (failure): Hemoglobin <8 g/dL or ANC <0.5x10^9/L or Platelets <20x10^9/L Lost Response: A lost response is captured by not meeting hematologic response criteria at a particular time point after having an initial response (complete, very good partial, or partial), or the need for additional treatment.
Measured: Randomization to 100 days, 180 days, 1 year and 2 years
Estimate the rates of failure of patients randomized to IST
Proportion of subjects with IST failure at 6 months (defined as Hemoglobin <8 g/dL or ANC <0.5x10^9/L or Platelets <20x10^9/L).
Measured: Randomization to 100 days, 180 days, 1 year and 2 years
Describe the secondary therapies given and outcomes achieved for patients failing initial therapy
Collect secondary therapies given for failure of primary randomized therapy (BMT after IST, second course of IST, second BMT). For the outcome after subsequent therapy, the median survival time will be estimated.
Measured: Randomization to 3-5 years
Comparison of rates of secondary MDS, AML, other subsequent neoplasms, and development of Paroxysmal Nocturnal Hemoglobinuria in both treatment arms for the duration of the trial.
Proportion of subjects in each treatment arm with i) subsequent neoplasms, ii) presence of a PNH clone at time of randomization who go on to develop symptomatic PNH through the duration of the protocol.
Measured: Randomization to 3-5 years
Comparison of HR-QoL score between patients randomized to both arms
Change in score between baseline and two years and the trajectory of change over all timepoints.
Measured: Randomization to 2 years post-randomization, randomization to up to 5 years post-randomization
Comparison of gonadal function values between patients randomized to both arms
Proportion of subjects with gonadal function values outside the expected percentile for that age.
Measured: Randomization to 1 year post-randomization, randomization to 2 years post-randomization, and randomization to up to 5 years post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2022
- Study start25 Jan 2023
- Primary completion6 Aug 2026
- Study completion6 Aug 2026
Why it stopped: Funding terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Unblinded, stratified, multi-center, phase 3, randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Center for International Blood and Marrow Transplant Research, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), North American Pediatric Aplastic Anemia Consortium, Pediatric Transplantation and Cellular Therapy Consortium, Blood and Marrow Transplant Clinical Trials Network
- Responsible party
- Principal investigator, David Williams, Boston Children's Hospital
- Investigators
- David Williams, MD, Principal investigator, Boston Children's HospitalMichael Pulsipher, MD, Principal investigator, University of UtahBronwen Shaw, MD, Principal investigator, CIBMTR/Medical College of Wisconsin (MCW)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05600426
- Sponsor's protocol ID
- IRB-2020-0438
- Other IDs
- 1UG3HL157564-01A1, 1U24HL157560-01A1
- Acronym
- TransIT
- Status last verified
- Oct 2026
- First submitted
- 20 Oct 2022
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Trial Comparing Unrelated Donor Bone Marrow Transplantation With Immune Suppressive Therapy for Newly Diagnosed Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)
- ClinicalTrials.gov ID
- NCT05600426
- Acronym / sponsor ID
- TransIT / IRB-2020-0438
- Conditions
- Severe Aplastic Anemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding terminated
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Center for International Blood and Marrow Transplant Research, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), North American Pediatric Aplastic Anemia Consortium, Pediatric Transplantation and Cellular Therapy Consortium, Blood and Marrow Transplant Clinical Trials Network
- Study start
- 25 Jan 2023 (actual)
- Primary completion
- 6 Aug 2026 (actual)
- Study completion
- 6 Aug 2026 (actual)
- First posted
- 31 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant. Regular 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 normally are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bone marrow transplant (BMT) is used as a secondary treatment in patients who did not get better with IST, had their disease come back, or a new worse disease replaced it (like leukemia).
This trial will compare time from randomization to failure of treatment or death from any cause of IST versus URD BMT when used as initial therapy to treat SAA.
The trial will also assess whether health-related quality of life and early markers of fertility differ between those randomized to URD BMT or IST, as well as assess the presence of marrow failure-related genes and presence of gene mutations associated with MDS or leukemia and the change in gene signatures after treatment in both study arms.
This study treatment does not include any investigational drugs. The medicines and procedures in this study are standard for treatment of SAA.
Detailed description
This study is a multi-center randomized phase III trial to compare the failure free survival between those randomized to IST vs 9-10/10 HLA matched URD BMT. The study will also address patient-reported outcomes and gonadal function in each arm and explore critical biological correlates including assessing germline genetic mutations associated with pediatric SAA that may lead to a predisposition to the disease and the risk of development of clonal hematopoiesis following IST vs BMT in pediatric and young adult SAA.
This clinical trial will randomize 234 children/AYA over 3.3-4.7 years at a 1:1 ratio between initial treatment with immune suppression therapy (IST) with horse ATG (hATG)/cyclosporine (CsA) versus well- matched (9-10/10 allele) unrelated donor (URD) bone marrow transplantation (BMT) using a regimen of rabbit ATG (rATG)/fludarabine/cyclophosphamide and 200 cGy TBI. Duration of subject participation for all study procedures in this study will be up to 2 years after treatment; a single later timepoint between 3 and 5 years will be collected to follow patients for specific protocol defined late effects and survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Unblinded, stratified, multi-center, phase 3, randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Immunosuppressive Therapy | Active comparator | Drug: cyclosporine, Drug: horse anti-thymocyte globulin (ATG), Procedure: Immunosuppressive Therapy (IST)Patient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine. |
| Matched Unrelated Stem Cell Transplant | Active comparator | Drug: cyclosporine, Procedure: Matched Unrelated Donor Hematopoetic Stem Cell Transplant, Drug: rabbit anti-thymocyte globulin (ATG), Drug: Methotrexate, Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: low-dose total body irradiation (TBI)Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention. |
Who may qualify
- Ages
- 0 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- To be eligible to participate in the randomized trial, an individual must meet all the following criteria:
- Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian.
- Age ≤25 years old at time of randomized trial consent.
- Confirmed diagnosis of idiopathic SAA, defined as:
- No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing).
Key exclusion criteria (10 listed)
- Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic isoamylase testing is not useful in children <3). Other testing per center may be performed to exclude IBMFS.
- Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.
- Known severe allergy to ATG.
- Prior allogeneic or autologous stem cell transplant.
- Prior solid organ transplant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclosporinecyclosporine | Drug | Immunosuppressive Therapy, Matched Unrelated Stem Cell Transplant |
| Matched Unrelated Donor Hematopoetic Stem Cell TransplantMatched Unrelated Donor (MUD) Hematopoietic Stem Cell Transplantation (HSCT) | Procedure or surgery | Matched Unrelated Stem Cell Transplant |
| horse anti-thymocyte globulin (ATG)Also: ATGAMhorse anti-thymocyte globulin (ATG) | Drug | Immunosuppressive Therapy |
| rabbit anti-thymocyte globulin (ATG)Also: thymoglobulinrabbit anti-thymocyte globulin (ATG) | Drug | Matched Unrelated Stem Cell Transplant |
| Methotrexatemethotrexate | Drug | Matched Unrelated Stem Cell Transplant |
| Fludarabinefludarabine | Drug | Matched Unrelated Stem Cell Transplant |
| Cyclophosphamidecyclophosphamide | Drug | Matched Unrelated Stem Cell Transplant |
| low-dose total body irradiation (TBI)low-dose total body irradiation (TBI) | Radiation | Matched Unrelated Stem Cell Transplant |
| Immunosuppressive Therapy (IST)Immunosuppressive Therapy (IST) | Procedure or surgery | Immunosuppressive Therapy |
Primary outcome
The primary endpoint of this trial is time from randomization to treatment failure or death from any cause.
Time frame: Randomization to 2 years post-randomization
The median time to failure or death will be compared on the two arms using the log-rank test. Failure of IST is defined as the date that a second definitive therapy was recommended (BMT, second course of ATG) and failure of BMT defined as the date that a second definitive therapy was recommended (second BMT, course of ATG).
27 secondary outcomes
Comparison of subjects with failure of IST or BMT before or at 2 years
Time frame: Randomization to 2 years post-randomization
Comparison of subjects with inadequate counts at 2 years among those who have not died or failed treatment.
Time frame: Randomization to 2 years post-randomization
Comparison of subjects on immune suppression therapy at 2 years among those who have not died or failed treatment.
Time frame: Randomization to 2 years post-randomization
Estimate the time from randomization to initiation of IST or BMT.
Time frame: Randomization through Day 100
Comparison of the frequency of failure to receive primary assigned therapy (IST or BMT) and reasons for the failure.
Time frame: Randomization through Day 100
Comparison of the incidence of bacteremia, viremia, and invasive fungal infection in the first two years after randomization in the IST and BMT arms.
Time frame: Randomization through two years post randomization
Estimate the median time to T- and B-cell immune reconstitution the first year for the URD BMT Arm
Time frame: Initiation of therapy (Day 0) to 100 days, 180 days, 1 year and 2 years
Comparison of overall survival at 1 and 2 years from randomization in both arms.
Time frame: Randomization to one year, randomization to two years
Comparison of treatment-related mortality (TRM) at 1 and 2 years from randomization in both arms.
Time frame: Randomization to 1 year, randomization to 2 years
Comparison of the median time from randomization to and rates of neutrophil recovery on both arms
Time frame: Randomization to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from randomization to and rate of platelet recovery on both arms
Time frame: Randomization to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from randomization to and rates of red blood cell recovery on both arms
Time frame: Randomization to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from initiation of therapy to and rates of neutrophil recovery on both arms
Time frame: Initiation of therapy to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from initiation of therapy to and rate of platelet recovery on both arms
Time frame: Initiation of therapy to 100 days, 180 days, 1 year and 2 years
Comparison of the median time from initiation of therapy to and rates of red blood cell recovery on both arms.
Time frame: Randomization to 100 days, 180 days, 1 year and 2 years
Estimate the rates of engraftment in patients who are randomized to URD BMT.
Time frame: Randomization to 3-5 years
Estimate the rates of primary graft failure in patients who are randomized to URD BMT .
Time frame: Randomization to 3-5 years
Estimate the rates of secondary graft failure in patients who are randomized to URD BMT .
Time frame: Randomization to 3-5 years
Estimate the rates of grade II-IV acute GVHD in patients who are randomized to URD BMT .
Time frame: Randomization to 3-5 years
Estimate the rates of grade III-IV acute GVHD in patients who are randomized to URD BMT.
Time frame: Randomization to 3-5 years
Estimate the rates of severe chronic GVHD in patients who are randomized to URD BMT.
Time frame: Randomization to 3-5 years
Estimate the rates of response of patients randomized to IST
Time frame: Randomization to 100 days, 180 days, 1 year and 2 years
Estimate the rates of failure of patients randomized to IST
Time frame: Randomization to 100 days, 180 days, 1 year and 2 years
Describe the secondary therapies given and outcomes achieved for patients failing initial therapy
Time frame: Randomization to 3-5 years
Comparison of rates of secondary MDS, AML, other subsequent neoplasms, and development of Paroxysmal Nocturnal Hemoglobinuria in both treatment arms for the duration of the trial.
Time frame: Randomization to 3-5 years
Comparison of HR-QoL score between patients randomized to both arms
Time frame: Randomization to 2 years post-randomization, randomization to up to 5 years post-randomization
Comparison of gonadal function values between patients randomized to both arms
Time frame: Randomization to 1 year post-randomization, randomization to 2 years post-randomization, and randomization to up to 5 years post-randomization
Results and safety
The study was stopped early (reason given: Funding terminated). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Williams, MD principal investigator
Boston Children's Hospital
Michael Pulsipher, MD principal investigator
University of Utah
Bronwen Shaw, MD principal investigator
CIBMTR/Medical College of Wisconsin (MCW)
52 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cyclosporine, Matched Unrelated Donor Hematopoetic Stem Cell Transplant and horse anti-thymocyte globulin (ATG) in people with Severe Aplastic Anemia, run by Boston Children's Hospital at 52 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 52 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Funding terminated). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint of this trial is time from randomization to treatment failure or death from any cause. (time frame: Randomization to 2 years post-randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.