AzTrials
AzTrials

Bone Marrow Failure SyndromePhase 2NCT04965597

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

A Phase 2 study testing Treosulfan, Fludarabine Phosphate and Tacrolimus in people with Bone Marrow Failure Syndrome and Congenital Amegakaryocytic Thrombocytopenia, run by Fred Hutchinson Cancer Center at 24 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 year to 49 years
What is being tested?
Treosulfan, Fludarabine Phosphate and Tacrolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
24 sitesUnited States
Study dates
19 Apr 2022to 18 Feb 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 49 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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:
Show all 101Show fewer
  • 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,
  • Reticulocytopenia, OR
  • Elevated adenosine deaminase activity, OR
  • Elevated hemoglobin F, OR
  • Macrocytosis, OR
  • Congenital anomalies
  • Indications for HCT:
  • Red blood cell (RBC) transfusion dependent anemia despite an adequate trial of steroids; OR
  • Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
  • Congenital Sideroblastic anemia
  • Criteria for Diagnosis:
  • A pathogenic mutation(s) for sideroblastic anemia
  • For those patients tested but lacking a genetic mutation:
  • Presence of ringed sideroblasts in the bone marrow excluding acquired causes of ringed sideroblasts such as lead poisoning \& zinc toxicity
  • Indications for HCT:
  • Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia OR
  • Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
  • GATA2 mutation with associated marrow failure
  • Criteria for Diagnosis:
  • A pathogenic mutation(s) for GATA2
  • Indications for HCT:
  • Severe neutropenia (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 ERC. In addition, patients with severe or recurrent infections will be reviewed by the ERC if they do not meet indications for transplant listed above
  • SAMD9 or SAMD9L disorders
  • Criteria for Diagnosis:
  • A pathogenic mutation(s) for SAMD9 or SAMD9L
  • Indications for HCT:
  • Severe neutropenia (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 ERC
  • Congenital amegakaryocytic thrombocytopenia
  • Criteria for Diagnosis:
  • A pathogenic mutation(s) for congenital amegakaryocytic thrombocytopenia.
  • For those patients tested but lacking a genetic mutation the patient must meet criteria below:
  • Thrombocytopenia early in life, AND
  • History of bone marrow demonstrating megakaryocyte hypoplasia
  • Indications for HCT:
  • Severe thrombocytopenia (platelet count < 20,000/uL) or transfusion-dependent thrombocytopenia, OR
  • Neutropenia defined as an ANC < 500/uL, OR
  • Severe anemia (hemoglobin < 8 g/dL) or transfusion-dependent anemia, OR
  • Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC
  • Paroxysmal nocturnal hemoglobinuria
  • Criteria for Diagnosis:
  • Paroxysmal nocturnal hemoglobinuria (PNH) clone size in granulocytes >= 10%, AND
  • Complement mediated intravascular hemolysis with an elevated LDH (above institutional upper limits of normal)
  • Indications for HCT:
  • PNH with thrombosis despite adequate medical management, OR
  • PNH with intravascular hemolysis requiring transfusion support despite adequate medical management, OR
  • Additional clinical or laboratory data may be considered for protocol eligibility following review by protocol 1904 ERC. In addition, patients with PNH and cytopenias may be considered for the protocol eligibility following review by protocol 1904 ERC
  • An undefined BMFD: a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified (excluding PNH) will be eligible for this clinical trial following approval by Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1904 ERC
  • A BMFD with a known genetic mutation but not listed above will be eligible for this clinical trial following approval by BMT CTN 1904 ERC
  • Patient and/or legal guardian must sign informed consent prior to initiation of conditioning for BMT CTN 1904
  • Note: The following patients MUST be reviewed by the BMT CTN 1904 ERC in order to determine if they are eligible for this trial:
  • All patients with Shwachman-Diamond syndrome, Diamond Blackfan anemia, congenital sideroblastic anemia, and congenital amegakaryocytic thrombocytopenia who have had genetic testing and a genetic mutation responsible for their disease was not identified
  • All patients with an undefined BMFD: a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified, excluding PNH
  • All patients with a BMFD and a known genetic mutation that is not listed above
  • All patients with GATA2 mutation and associated marrow failure
  • All patients with SAMD9 or SAMD9L disorders
  • There may be circumstances where a treating physician will consider a transplant for a patient with a BMFD who does not meet all the criteria listed under "indications for HCT". In these situations, treating physicians may submit their patient to the BMT CTN 1904 ERC for review in order to determine if the patient is eligible for this clinical trial based on additional clinical or laboratory information
  • Many patients with BMFD can have bone marrow evaluations that raise concern for possible myelodysplastic syndrome (MDS) including but not limited to dysplastic bone marrow evaluations or cytogenetic abnormalities. However, in patients BMFD these findings are not necessarily diagnostic or consistent with MDS. Therefore, given the complexities of diagnosing MDS in patients with BMFD, all patients with bone marrow evaluations concerning for possible MDS should be submitted to the ERC for review to confirm or exclude MDS. This is particularly important as we do not want to exclude potentially eligible patients due to an incorrect diagnosis of MDS
  • HLA-MATCHED RELATED DONOR: HLA-matched sibling: Must be a minimum HLA-6/6 matched to the recipient at HLA-A, -B (serologic typing) and DRB1 (high-resolution typing)
  • HLA-MATCHED RELATED DONOR: HLA-matched related (phenotypic match): Fully matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing.
  • HLA-MATCHED RELATED DONOR: If a genetic mutation is known for the patient, the HLA-matched related donor [either HLA-matched sibling or HLA-matched related (phenotypic match)] must be screened for the same genetic mutation if clinically appropriate and should be confirmed to not have the same genetic disease (this does not include patients with PNH). Consult the protocol team with questions
  • HLA-MATCHED RELATED DONOR: If a patient has an undefined BMFD (a patient with a BMFD for whom a genetic mutation responsible for their bone marrow failure phenotype has not been identified), the HLA-matched related donor [either HLA-matched sibling or HLA-matched related (phenotypic match)] must have an evaluation as directed by the treating physician to confirm that the donor does not have the same underlying disease. This will include a complete blood count (CBC) with differential and potentially a bone marrow evaluation or other studies as directed by the treating physician
  • UNRELATED DONOR: Fully matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing OR
  • UNRELATED DONOR: Mismatched for a single HLA-class 1 allele (HLA-A, -B, or -C) by high-resolution typing; OR
  • UNRELATED DONOR: Mismatched for a single HLA DQB1 allele or antigen by high-resolution typing
  • Note: donor patient (DP) matching per institutional practice
  • DONOR SELECTION RECCOMENDATIONS: in the case where there are multiple donor options, donors should be selected based on the following priority numbered below:
  • Unaffected fully HLA-matched sibling
  • Unaffected fully phenotypically HLA-matched related donor
  • Fully HLA-matched unrelated donor
  • Unrelated donor with single allele or antigen level mismatch at DQB1
  • Unrelated donor with single allele level mismatch at class 1 (HLA-A, -B, or -C)

Who cannot join

  • 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
Show all 29Show fewer
  • 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
  • Females who are pregnant or breast-feeding
  • Females and males of childbearing potential who are unwilling to practice an effective method of contraception or agree to abstinence from the time of signing informed consent through 12 months post-transplant or off tacrolimus whichever is later
  • Known hypersensitivity to treosulfan or fludarabine
  • Known life-threatening reaction (i.e. anaphylaxis) to Thymoglobulin that would prohibit use for the patient as this study requires use of the Thymoglobulin preparation of anti-thymocyte globulin (ATG)

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

United States24 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins University

    Baltimore, Maryland, 21231

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14203

  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Medical College of Wisconsin/Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Cohen Children's Hospital of NY

    Queens, New York, 11040

  • Primary Children's/University of Utah

    Salt Lake City, Utah, 84113

  • Rady Children's Hospital/UCSD

    San Diego, California, 92123

  • University of California San Francisco

    San Francisco, California, 94143

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • St. Louis Children's Hospital

    St Louis, Missouri, 63110

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Treosulfan, Fludarabine Phosphate, Tacrolimus, Methotrexate, Lapine T-Lymphocyte Immune Globulin
Keywords
Bone Marrow Failure Disorders, HSCT, Treosulfan, Unrelated donor, Matched donor, mismatched donor, transplant
Medical subject headings
Bone Marrow Failure Disorders, Congenital amegakaryocytic thrombocytopenia, Anemia, Diamond-Blackfan, Anemia, Hypochromic, Hemoglobinuria, Paroxysmal, Shwachman-Diamond Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TreosulfanDrug

    Also called Dihydroxybusulfan, Ovastat, Treosulphan, Tresulfon

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, 9H-purin-6-amine, 2-fluoro-9-(5-O-phosphono-beta-D-arabinofuranosyl), Beneflur

    Given IV

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV and PO

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • Lapine T-Lymphocyte Immune GlobulinBiological

    Also called Anti-Thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte Globulin

    Given IV

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT

    Undergo PBSC

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    Also called Allo BMT, Allogeneic Blood and Marrow Transplantation, Allogeneic BMT

    Undergo bone marrow transplant

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo ECHO

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Bone Marrow BiopsyProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection

    Undergo blood sample collection

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology

    Undergo chest x-ray

  • Computed TomographyProcedure or surgery

    Also called Computed Axial Tomography, CAT Scan, CT Scan

    Undergo chest CT

Study groups in NCT04965597
Study groupRoleWhat they receive
Treatment (conditioning regimen; transplant; GVHD prophylaxis)ExperimentalCONDITIONING REGIMEN: Patients receive treosulfan IV over 120 minutes on days -6 to -4, fludarabine phosphate IV over 60 minutes on days -6 to -2, and 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 PO. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Patients undergo ECHO or MUGA as well as possible x-ray or CT at baseline and undergo bone marrow biopsy and aspiration at baseline and follow up. Patients also undergo blood sample collection throughout the trial.
Receives: Drug: Treosulfan; Drug: Fludarabine Phosphate; Drug: Tacrolimus; Drug: Methotrexate; Biological: Lapine T-Lymphocyte Immune Globulin; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Allogeneic Bone Marrow Transplantation; Other: Quality-of-Life Assessment; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection; Procedure: X-Ray Imaging; Procedure: Computed Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Graft-Versus Host-Disease (GVHD)-Free Event-Free Survival (EFS)

    The primary endpoint is the incidence of 1-year GVHD free, EFS (GEFS). An event is defined as death due to any cause, primary or secondary graft failure/rejection, or 2nd HCT whichever occurs first. Grade III-IV acute GVHD and chronic GVHD (using National Institutes of Health [NIH] consensus criteria) requiring systemic immune suppression will be considered in this estimate.

    Measured: 1 year post-HCT

Secondary outcomes (20)

  1. Overall Survival

    Overall survival at day 100 after HCT

    Measured: Day 100 post-HCT

  2. Overall Survival

    Overall survival at 6 months after HCT

    Measured: 6 months post-HCT

  3. Overall Survival

    Overall survival at 1 year after HCT

    Measured: 1 year post-HCT

  4. Event-Free Survival

    Event-free survival will be estimated at 12 months after HCT. An event is defined as death due to any cause, primary or secondary graft failure/rejection, or 2nd HCT, whichever occurs first

    Measured: 1 year post-HCT

  5. Hematologic Recovery: Neutrophil recovery

    Hematologic recovery will be assessed according to neutrophil recovery after transplant. Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ to 500/mm3 for 3 consecutive measurements on 3 different days. The first of the three days will be designated the day of neutrophil recovery. The competing event is death without neutrophil recovery.

    Measured: Assessed up to 1 year post-HCT

  6. Hematologic Recovery: Platelet recovery

    Hematologic recovery will be assessed according to platelet counts recovery after transplant. Platelet recovery is defined as the first day of a minimum of 3 days that the patient has a sustained platelet count ≥ 20,000/mm3 with no platelet transfusions in the preceding 7 days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment.

    Measured: Day 100 post-HCT

  7. Donor Chimerism (CD3 and Myeloid)

    Proportions of patients with full (>95%), mixed (5-95%), or rejection (<5%) myeloid

    Measured: Day 28 post-HCT

  8. Donor Chimerism (CD3 and Myeloid)

    Proportions of patients with full (>95%), mixed (5-95%), or rejection (<5%) myeloid

    Measured: Day 100 post-HCT

  9. Donor Chimerism (CD3 and Myeloid)

    Proportions of patients with full (>95%), mixed (5-95%), or rejection (<5%) myeloid

    Measured: 1 year post-HCT

  10. Primary graft failure/rejection

    Defined as never achieving ANC ≥ 500/μL or never achieving ≥ 5% donor myeloid chimerism assessed by peripheral blood chimerism assays by day +42 post-HCT. Second infusion of hematopoietic cells is also considered indicative of primary graft failure by day +42 post-HCT

    Measured: Day 42 post-HCT

  11. Secondary graft failure/rejection post-HCT

    Defined as < 5% donor myeloid chimerism in peripheral blood beyond day +42 post-HCT in patients with prior documentation of hematopoietic recovery with ≥ 5% donor cells by day +42 post-HCT. Second infusion of hematopoietic cells is also considered indicative of secondary graft failure.

    Measured: Assessed up to 1 year post-HCT

  12. Grade II-IV and grade III-IV GVHD at day 100

    The cumulative incidences of acute grade II-IV and III-IV GVHD at day 100 after HCT will be determined.

    Measured: Day 100 post-HCT

  13. Grade II-IV and grade III-IV GVHD at day 180

    The cumulative incidences of acute grade II-IV and III-IV GVHD at day 100 after HCT will be determined.

    Measured: Day 180 post-HCT

  14. Chronic GVHD

    The cumulative incidence of chronic GVHD (using NIH consensus criteria) requiring systemic immune suppression at 1 year after HCT will be determined. Data will be collected directly from providers and chart review as defined by the NIH Consensus Conference Criteria

    Measured: 1 year post-HCT

  15. Incidence of grade 3-5 toxicities

    Grade 3-5 toxicities by day 30 after HCT

    Measured: Day 30 post-HCT

  16. Incidence of grade 3-5 toxicities

    Grade 3-5 toxicities by day 100 after HCT

    Measured: Day 100 post-HCT

  17. Incidence of grade 2-3 systemic infections

    All microbiologically documented infections or significant infections requiring antibiotic/antifungal therapy occurring up to 6 months after HCT

    Measured: 6 months post-HCT

  18. Incidence of Epstein Barr virus (EBV) reactivation requiring therapy

    The incidence of EBV reactivation requiring therapy in the first 180 days after HCT, and of EBV-associated lymphoproliferative disorder in the first 180 days after HCT will be evaluated.

    Measured: Day 180 post-HCT

  19. Incidence of EBV-associated lymphoproliferative disorder

    Measured: Day 180 post-HCT

  20. Incidence of cytomegalovirus (CMV) reactivation requiring therapy by day 180 post-HCT

    Measured: Up to day 180 post-HCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2021
  2. Study start19 Apr 2022
  3. Primary completion18 Feb 2026
  4. Study completion18 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04965597
Sponsor's protocol ID
BMTCTN1904
Other IDs
2U10HL069294-11, RG1121820, 10840, NCI-2021-13862
Status last verified
Mar 2026
First submitted
21 Jun 2021
Last updated
9 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Treosulfan, Fludarabine Phosphate and Tacrolimus in people with Bone Marrow Failure Syndrome and Congenital Amegakaryocytic Thrombocytopenia, run by Fred Hutchinson Cancer Center at 24 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 101 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Graft-Versus Host-Disease (GVHD)-Free Event-Free Survival (EFS) (time frame: 1 year post-HCT). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04965597.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2026; AzTrials last refreshed its copy on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in