NCT04965597

Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)

Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for the Treatment of Bone Marrow Failure Diseases

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 1 Year – 49 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests whether treosulfan, fludarabine, and rabbit antithymocyte globulin (rATG) work when given before a blood or bone marrow transplant (conditioning regimen) to cause fewer complications for patients with bone marrow failure diseases. Chemotherapy drugs, such as treosulfan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Fludarabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. rATG is used to decrease the body's immune response and may improve bone marrow function and increase blood cell counts. Adding treosulfan to a conditioning regimen with fludarabine and rATG may result in patients having less severe complications after a blood or bone marrow transplant.

Detailed description

OUTLINE: CONDITIONING REGIMEN: Patients receive treosulfan intravenously (IV) over 120 minutes on days -6 to -4, fludarabine phosphate IV over 60 minutes on days -6 to -2, and lapine T-lymphocyte immune globulin (rATG) IV over 4-6 hours on days -4 to -2. TRANSPLANTATION: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously beginning on day -2 and a taper beginning on day 180. Patients may also receive tacrolimus orally (PO). Patients also receive methotrexate IV on days 1, 3, 6, and 11. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) as well as possible chest radiography (x-ray) or computed tomography (CT) at baseline and undergo bone marrow biopsy and aspiration at baseline and follow up. Patients also undergo blood sample collection throughout the trial. After completion of study treatment, patients are followed up at 1 year from transplant.

Conditions

• Bone Marrow Failure Syndrome
• Congenital Amegakaryocytic Thrombocytopenia
• Diamond-Blackfan Anemia
• Hereditary Sideroblastic Anemia
• Paroxysmal Nocturnal Hemoglobinuria
• Shwachman-Diamond Syndrome
• Hematologic Neoplasm With Germline GATA2 Mutation
• Hematologic Neoplasm With Germline SAMD9 Mutation
• Hematologic Neoplasm With Germline SAMD9L Mutation

Interventions

Type	Name	Description
DRUG	Treosulfan	Given IV
DRUG	Fludarabine Phosphate	Given IV
DRUG	Tacrolimus	Given IV and PO
DRUG	Methotrexate	Given IV
BIOLOGICAL	Lapine T-Lymphocyte Immune Globulin	Given IV
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo PBSC
PROCEDURE	Allogeneic Bone Marrow Transplantation	Undergo bone marrow transplant
OTHER	Quality-of-Life Assessment	Ancillary studies
PROCEDURE	Echocardiography	Undergo ECHO
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and aspiration
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow biopsy and aspiration
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	X-Ray Imaging	Undergo chest x-ray
PROCEDURE	Computed Tomography	Undergo chest CT

Timeline

• Start date: 2022-04-19
• Primary completion: 2026-02-18
• Completion: 2026-02-18
• First posted: 2021-07-16
• Last updated: 2026-03-09

Locations

24 sites across 1 country: United States

Regulatory

• FDA-regulated drug study