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

Completed · Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT04965597

Run by

Fred Hutchinson Cancer Center

People needed

40

Starts

2022-04-19

Expected to finish

2026-02-18

Last updated by the study team

2026-03-09

Who can join

Age: 1 and older, up to 49. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patient must be >= 1.0 year of age and less than 50.0 years of age at the time of enrollment (i.e. patient must have celebrated their 1st birthday when enrolled and must NOT have celebrated their 50th birthday when enrolled; 49.99 years)
• Underlying BMFD treatable by allogenic HCT
• Shwachman-Diamond syndrome
• Criteria for Diagnosis:
• A pathogenic mutation(s) for Shwachman-Diamond syndrome
• For those patients tested but lacking a genetic mutation they must meet both *** criteria below:
• Exocrine pancreatic dysfunction as defined by at least one of the following:
• Pancreatic isoamylase below normal (age >= 3 years old), OR
• Fecal elastase < 200, AND
• Bone marrow failure as evidence by at least one of the following:
• Intermittent or persistent neutropenia (absolute neutrophil count < 1,500/uL), OR
• Hypo-productive anemia with a hemoglobin concentration below the age-related adjusted norms, OR
• Unexplained macrocytosis, OR
• Platelet count < 150,000/uL without alternative etiology, OR
• Hypocellular bone marrow
• Indications for HCT:
• Severe neutropenia (absolute neutrophil count [ANC] < 500/uL), OR
• Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
• Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
• Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 eligibility review committee (ERC). In addition, patients with severe or recurrent infections will be reviewed by the ERC if they do not meet the indications for transplant listed above
• Diamond Blackfan Anemia
• Criteria for Diagnosis:
• A pathogenic mutation for Diamond Blackfan anemia
• For those patients tested but lacking a genetic mutation the patient must meet the first *** criteria and at least one of the subsequent *** criteria listed below:
• History of deficiency of erythroid precursors in an otherwise cellular bone marrow AND,

You may not qualify if…

• Patients with idiopathic aplastic anemia, Fanconi anemia, dyskeratosis congenita, and congenital neutropenia
• Patients with MDS as defined by the World Health Organization (WHO) or leukemia
• Prior allogeneic HCT
• Patient's weight =< 10.0 kg (actual body weight and adjusted body weight) at time of study enrollment
• Lansky (patients < 16 years of age) or Karnofsky (patients >= 16 years of age) performance < 70%
• Left ventricular ejection fraction < 50% by echocardiogram or multi-gated acquisition (MUGA) scan
• For patients unable to obtain a left ventricular ejection fraction, left ventricular shortening fraction of < 26%
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) < 50%, forced expiratory volume (FEV)1 < 50% predicted, and forced vital capacity (FVC) < 50% predicted
• For patients unable to perform pulmonary function tests (PFTs) due to age or developmental delay: oxygen (O2) saturation < 92% on room air
• On supplemental oxygen
• Estimated creatinine clearance < 60 mL/minute/1.73m\^2 (estimated per institutional practice)
• Dialysis dependent
• Conjugated bilirubin > 2 x upper limit of normal for age (ULN, unless attributable to Gilbert's syndrome)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 4 x ULN for age, or
• Fulminant liver failure or cirrhosis
• Iron overload - This exclusion criterion only applies to patients who are considered at risk for hepatic or cardiac iron overload. Therefore, not all patients enrolled on this protocol will undergo formal hepatic or cardiac iron assessment
• For patients with a history of significant transfusions defined as >= 8 packed red blood cell transfusions per year for >= 1 year or have received >= 20 packed red blood cell transfusions (lifetime cumulative) will require formal hepatic and cardiac iron measurement. In addition, patients with a prior history of hepatic or cardiac iron overload will also require formal assessment for iron overload. Patients are excluded if:
• Hepatic iron content >= 8 mg Fe/g dry weight by liver magnetic resonance imaging (MRI) using a validated methodology (such as T2 * MRI or ferriscan) or liver biopsy per institutional practice
• Cardiac iron content < 25 msec by cardiac T2 * MRI
• Uncontrolled bacterial infection within 1 week of study enrollment. Uncontrolled is defined as currently taking medication with no clinical improvement or progression on adequate medical treatment
• Uncontrolled viral or fungal infection within 30 days of study enrollment. Uncontrolled is defined as currently taking medication with no clinical improvement or progression on adequate medical treatment
• Positive for human immunodeficiency virus (HIV)
• Presence of clinically significant anti-donor human leukocyte antigen (HLA)-antibodies per institutional practice
• Prior solid organ transplant
• Patients with prior malignancies except resected non-melanoma skin cancer or treated cervical carcinoma in situ

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• Rady Children's Hospital/UCSD — San Diego, California, United States
• University of California San Francisco — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Boston Children's Hospital — Boston, Massachusetts, United States
• University of Michigan Medical Center — Ann Arbor, Michigan, United States
• University of Minnesota — Minneapolis, Minnesota, United States
• St. Louis Children's Hospital — St Louis, Missouri, United States
• Roswell Park Comprehensive Cancer Center — Buffalo, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Cohen Children's Hospital of NY — Queens, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Cincinnati Children's Hospital — Cincinnati, Ohio, 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
• Vanderbilt University Medical Center — Nashville, Tennessee, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• Texas Children's Hospital — Houston, Texas, United States
• Primary Children's/University of Utah — Salt Lake City, Utah, United States
• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States
• Medical College of Wisconsin/Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

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