NAPAAC Clinical Trials and Studies

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

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 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.

 Publications from other Trials/Studies:

​Shimano KA, Narla, A, Rose MJ, Gloude NJ, Allen SW, Bergstrom K, Broglie L, Carella BA, Castillo P, de Jong JLO, Dror Y, Geddis AE, Huang JN, Lau BW, McGuinn C, Nakano TA, Overholt K, Rothman JA, Sharathkumar A, Shereck E, Vlachos A, Olson TS, Bertuch AA, Wlodarski MW, Shimamura A, Boklan J. Diagnostic work-up for severe aplastic anemia in children: Consensus of the North American Pediatric Aplastic Anemia Consortium. American Journal of Hematology. 2021 Nov 1;96(11):1491-1504. doi: 10.1002/ajh.26310.Epub 2021 Aug 20. PMID: 34342889

Pulsipher MA, Lehmann LE, Bertuch AA, Sasa G, Olson T, Nakano TA, Gillio A, Burroughs LM, Lipton JM, Huang JN, Dickerson KE, Bertaina A, Zhuang C, Malsch M, Fleming M, Weller E, Shimamura A, Williams DA​. A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune‐suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of the North American Pediatric Aplastic Anemia Consortium and the Pediatric Transplantation and Cellular Therapy Consortium​. ​Pediatr Blood Cancer. 2020 Oct;67(10):e28444. doi: 10.1002/pbc.28444.Epub 2020 Aug 9. PMID: 32776425

Nakano TA, Lau BW, Dickerson KE, Wlodarski MW, Pollard J, Shimamura A, Hofmann I, Sasa G, Elghetany T, Cada M, Dror Y, Ding H, Allen SW, Hanna R, Campbell K, Olson, TS. Diagnosis and treatment of pediatric myelodysplastic syndromes: A survey of the North American Pediatric Aplastic Anemia Consortium. Pediatr Blood Cancer. 2020 Oct;67(10):e28652. doi: 10.1002/pbc.28652.Epub 2020 Aug 11. PMID: 32779892

Rogers ZR, Nakano TA, Olson TS, Bertuch AA, Wang W, Gillio A, Coates TD, Chawla A, Castillo P, Kurre P, Gamper C, Bennett CM, Joshi S, Geddis AE, Boklan J, Nalepa G, Rothman JA, Huang JN, Kupfer GM, Cada M, Glader B, Walkovich KJ, Thompson AA, Hanna R, Vlachos A, Malsch M, Weller EA, Williams DA, and Shimamura A. Immunosuppressive therapy for pediatric aplastic anemia: a North American Pediatric Aplastic Anemia Consortium study. Haematologica. 2019 Oct;104(10):1974-1983. doi: 10.3324/haematol.2018.206540. Epub 2019 Apr 4. PMID: 30948484

Williams DA, Bennett C, Bertuch A, Bessler M, Coates T, Corey S, Dror Y, Huang J, Lipton J, OlsonTS, Reiss UM, Rogers ZR, Sieff C, Vlachos A, Walkovich K, Wang W, Shimamura A. Diagnosis and Treatment of Pediatric Acquired Aplastic Anemia (AAA): an Initial Survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC). Pediatr Blood Cancer. 2013 Nov 27;61(5):869–874. doi: 10.1002/pbc.24875. PMID: 24285674

Shimamura A, Maschan A, Bennett C, Samarasinghe S, Farrar JE, Li CK, Sirachainan N, Pongtanakul B, Komvilaisak P, Zubarovskaya L, Rothman JA, Walkovich K, Nakano TA, Bertuch AA, Ferrao A, Bhat R, Hanna R, Overholt K, Boklan J, Wong TF, Wang Q, Urban P, Strahm B, Wang W, Vlachos A, Williams DA. Eltrombopag in combination with immunosuppressive therapy in pediatric severe aplastic anemia: phase 2 ESCALATE trial. Blood Adv. 2025 Aug 12;9(15):3728-3738. doi: 10.1182/bloodadvances.2024015102.
PMID: 40315366