Summary

Eligibility
for people ages 0-25 (full criteria)
Location
at Oakland, California and other locations
Dates
study started
completion around
Principal Investigator
by Nahal Lalefar, MDKristin Shimano, MD
Headshot of Nahal Lalefar
Nahal Lalefar

Description

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.

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)

Details

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.

Keywords

Severe Aplastic Anemia, Anemia, Aplastic Anemia, Cyclosporine, Cyclophosphamide, Methotrexate, Fludarabine, Cyclosporins, Thymoglobulin, Antilymphocyte Serum, Immunosuppressive Agents, Matched Unrelated Donor Hematopoetic Stem Cell Transplant, horse anti-thymocyte globulin (ATG), rabbit anti-thymocyte globulin (ATG), low-dose total body irradiation (TBI), Immunosuppressive Therapy (IST), Immunosuppressive Therapy, Matched Unrelated Stem Cell Transplant

Eligibility

You can join if…

Open to people ages 0-25

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 109/L, platelets <20 x 109/L, absolute reticulocyte count <60 x 109/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.

You CAN'T join if...

  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

Locations

  • Children's Hospital & Research Center Oakland accepting new patients
    Oakland California 94609 United States
  • UCSF accepting new patients
    San Francisco California 94158 United States
  • Stanford accepting new patients
    Palo Alto California 94304 United States

Lead Scientists at UCSF

  • Nahal Lalefar, MD
    Nahal Rose Lalefar, MD, is an associate professor of pediatrics who specializes in pediatric hematology/oncology with a focus on stem cell transplantation. She runs the bone marrow transplant long term follow up program at UCSF Benioff Children's Hospital Oakland. She also runs a hematology clinic at UCSF-Fresno.
  • Kristin Shimano, MD
    Professor, Pediatrics, School of Medicine. Authored (or co-authored) 53 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Boston Children's Hospital
ID
NCT05600426
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 234 study participants
Last Updated