A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)

NCT ID: NCT05600426

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-25
• Study Completion Date: 2029-12-31

Brief 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. 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.

Conditions

Severe Aplastic Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immunosuppressive Therapy

Patient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine.

Group Type: ACTIVE_COMPARATOR

cyclosporine

Intervention Type: DRUG

cyclosporine

horse anti-thymocyte globulin (ATG)

Intervention Type: DRUG

horse anti-thymocyte globulin (ATG)

Immunosuppressive Therapy (IST)

Intervention Type: PROCEDURE

Immunosuppressive Therapy (IST)

Matched Unrelated Stem Cell Transplant

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.

Group Type: ACTIVE_COMPARATOR

cyclosporine

Intervention Type: DRUG

cyclosporine

Matched Unrelated Donor Hematopoetic Stem Cell Transplant

Intervention Type: PROCEDURE

Matched Unrelated Donor (MUD) Hematopoietic Stem Cell Transplantation (HSCT)

rabbit anti-thymocyte globulin (ATG)

Intervention Type: DRUG

rabbit anti-thymocyte globulin (ATG)

Methotrexate

Intervention Type: DRUG

methotrexate

Fludarabine

Intervention Type: DRUG

fludarabine

Cyclophosphamide

Intervention Type: DRUG

cyclophosphamide

low-dose total body irradiation (TBI)

Intervention Type: RADIATION

low-dose total body irradiation (TBI)

Interventions

cyclosporine

cyclosporine

Intervention Type: DRUG

Matched Unrelated Donor Hematopoetic Stem Cell Transplant

Matched Unrelated Donor (MUD) Hematopoietic Stem Cell Transplantation (HSCT)

Intervention Type: PROCEDURE

horse anti-thymocyte globulin (ATG)

horse anti-thymocyte globulin (ATG)

Intervention Type: DRUG

rabbit anti-thymocyte globulin (ATG)

rabbit anti-thymocyte globulin (ATG)

Intervention Type: DRUG

Methotrexate

methotrexate

Intervention Type: DRUG

Fludarabine

fludarabine

Intervention Type: DRUG

Cyclophosphamide

cyclophosphamide

Intervention Type: DRUG

low-dose total body irradiation (TBI)

low-dose total body irradiation (TBI)

Intervention Type: RADIATION

Immunosuppressive Therapy (IST)

Immunosuppressive Therapy (IST)

Intervention Type: PROCEDURE

Other Intervention Names

ATGAM; thymoglobulin

Eligibility Criteria

Inclusion Criteria

To be eligible to participate in the randomized trial, an individual must meet all the following criteria:

1. Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian.

2. Age ≤25 years old at time of randomized trial consent.

3. Confirmed diagnosis of idiopathic SAA, defined as:

1. Bone marrow cellularity <25%, or <30% hematopoietic cells.

2. 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.

4. 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).

5. 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).

6. In the treating physician's opinion, no obvious contraindications precluding them from BMT or IST.

Exclusion Criteria

1. 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.

2. Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.

3. Known severe allergy to ATG.

4. Prior allogeneic or autologous stem cell transplant.

5. Prior solid organ transplant.

6. Infection with human immunodeficiency virus (HIV).

7. Active Hepatitis B or C. This only needs to be excluded in patients where there is clinical suspicion of hepatitis (e.g., elevated LFTs).

8. Female patients who are pregnant or breast-feeding.

9. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.

10. 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

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center for International Blood and Marrow Transplant Research

NETWORK

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

North American Pediatric Aplastic Anemia Consortium

UNKNOWN

Sponsor Role: collaborator

Pediatric Transplantation and Cellular Therapy Consortium

OTHER

Sponsor Role: collaborator

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

David Williams

Chief - Division of Hematology/Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Williams, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Michael Pulsipher, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Bronwen Shaw, MD

Role: PRINCIPAL_INVESTIGATOR

CIBMTR/Medical College of Wisconsin (MCW)

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Phoenix Children's Hospital

Phoenix, Arizona, United States

Arkansas

Little Rock, Arkansas, United States

Loma Linda

Loma Linda, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

UCLA

Los Angeles, California, United States

Children's Hospital & Research Center Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

Stanford

Palo Alto, California, United States

Rady Children's Hospital San Diego

San Diego, California, United States

University of California San Francisco

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

Nemours Children's Hospital, Delaware

Wilmington, Delaware, United States

Children's National Hospital

Washington D.C., District of Columbia, United States

University of Florida

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Children's Hospital of Atlanta/Emory

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Indiana University Hospital/Riley Hospital for Children

Indianapolis, Indiana, United States

Children's Hospital NOLA

New Orleans, Louisiana, United States

Maine Health

Scarborough, Maine, United States

Boston Children's Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Mayo Clinic Rochestser

Rochester, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Washington University in St. Louis

St Louis, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Columbia University Medical Center

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Levine Children's Hospital

Charlotte, North Carolina, United States

Duke University

Durham, North Carolina, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Children's Medical Center Dallas

Dallas, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Methodist Healthcare

San Antonio, Texas, United States

University of Utah/Primary Children's Hospital

Salt Lake City, Utah, United States

Children's Hospital of the King's Daughter

Norfolk, Virginia, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

University of Wisconsin

Madison, Wisconsin, United States

British Columbia Children's

Vancouver, British Columbia, Canada

Winnipeg CancerCare Manitoba

Winnipeg, Manitoba, Canada

Countries

United States; Canada

Other Identifiers

1UG3HL157564-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1U24HL157560-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-2020-0438

Identifier Type: -

Identifier Source: org_study_id