A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Subjects With VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) Syndrome

  • End date
    Jul 1, 2025
  • participants needed
  • sponsor
    National Cancer Institute (NCI)
Updated on 21 October 2022
total body irradiation
mycophenolate mofetil
allogeneic hematopoietic stem cell transplant



Allogeneic hematopoietic stem cell transplant involves taking blood stem cells from a donor and giving them to a recipient. The transplants are used to treat certain diseases and cancers. Researchers want to see if the transplant can treat VEXAS Syndrome.


To see if stem cell transplants can be successfully performed in people with VEXAS and even improve the disease.


People ages 18-75 who have VEXAS Syndrome that has caused significant health problems and standard treatment either has not worked or is not available.


Participants will be screened with:

Physical exam

Medical review

Blood and urine tests

Heart and lung function tests

Bone marrow biopsy

Participants will have a chest x-ray. They will have an imaging scan of the head, chest, abdomen, pelvis, and sinus. They will have a bone density scan. They will have a dental exam and eye exam. They will meet with specialists. They will repeat some screening tests.

Participants will be admitted to the NIH hospital. They have a central venous catheter put into a vein in the chest or neck. They will receive drugs to prepare their bone marrow for the transplant. They may have total body irradiation. They will receive the donor stem cells through the catheter. They will get other drugs to prevent complications and infections. After discharge, they must stay in the DC area for 3 months for weekly study visits.

Participants will have study visits 30, 60, 100, 180, 210, 240, 300, and 360 days later. After that, they will have yearly visits for 2 years and then be contacted yearly by phone....



In 2019, investigators at the National Institutes of Health defined a new disease syndrome named VEXAS: Vacuoles in bone marrow cells, E1 enzyme mutations, X-linked, Autoinflammatory, Somatic syndrome. This syndrome is characterized by inflammatory and hematologic features and is frequently accompanied by marrow dysplasia, progressive bone marrow failure, and in some cases, the development of overt myelodysplastic syndrome (MDS) or other myeloid neoplasms. Somatic mutations are present at methionine 41 in UBA1, an X-linked gene encoding the major E1 ubiquitin activating enzyme that initiates the majority of cellular ubiquitylation.

The inflammatory features of VEXAS include fever, pulmonary infiltrates, skin lesions, ear and nose chondritis, musculoskeletal involvement, and elevated inflammatory markers. The hematologic features include cytopenia, characteristic vacuoles in myeloid and erythroid precursors cells, and dysplastic bone marrow. Patients included in the initial description of the syndrome fulfill clinical or classification criteria for both inflammatory diseases (relapsing polychondritis, Sweet syndrome, polyarteritis nodosa, giant cell arteritis) and hematologic conditions (MDS, myeloid neoplasms or plasma cell dyscrasia). The inflammatory features of VEXAS are refractory to treatment other than high doses of glucocorticoids. Increased mortality and frequent morbidity are common in VEXAS secondary to the disease and treatment-related complications. The clinical manifestations of VEXAS are time-dependent. Systemic inflammation typically precedes progressive bone marrow failure with or without the development of hematologic malignancies leading to death. Escalating doses of glucocorticoids are typically administered to control the refractory, progressive features of systemic inflammation. Worsening cytopenias often require transfusion support.

The discovery of hematologic mosaicism as the genetic driver of rheumatologic/hematologic syndromes defines a novel class of diseases, termed hematoinflammatory diseases (HINDS), and it raises the possibility that therapies aimed at eradicating these clones may be efficacious in this patient population.


Primary Objectives:

To determine whether allogeneic hematopoietic stem cell transplantation (HSCT) results in sustained donor engraftment at day 100 and one-year post-HSCT.

To determine whether allogeneic HSCT results in reversal of the clinical phenotype of VEXAS at one year and two years post-HSCT without requiring interval prednisone at >= 0.5 mg/kg per day for reasons other than graft-versus-host disease (GVHD).


Recipients ages 18-75 year-old with or without a somatic mutation in UBA1 who have: 1) the clinical phenotype for VEXAS with refractory cutaneous, pulmonary, musculoskeletal, and/or other recurrent acute inflammatory manifestations, and 2) require >= 0.5 mg/kg per day of prednisone for inflammatory manifestations OR have cytopenia (transfusion dependent anemia, transfusion dependent thrombocytopenia/platelets <75,000, neutropenia <1,000/microL) or myeloid neoplasm (by WHO criteria) or being intolerant or refractory to use steroids.

Have an 8/8 or 7/8 HLA-matched related or unrelated donor, or a haploidentical related donor.


For Recipients with 8/8 HLA Matched Donors:

Participants will receive reduced intensity conditioning with the following regimen: fludarabine 40 mg/m^2 IV once daily for four days on days -6, -5, -4, -3 and Busulfan IV for three days on days -6, -5, -and -4 followed by HSCT on day 0. The busulfan dose will be based on pharmacokinetic levels from the test dose or real time PKs and will be targeted to an AUC of 3600-4800 micorMolmin/L (52-65 mgh/L) (3.2 mg/kg IV per day will be the default dose).

For Recipients with 7/8 HLA Matched Donors or Haploidentical Related Donors:

Participants will receive reduced intensity conditioning with the following regimen: fludarabine 30 mg/m^2 IV once daily for five days on days -6, -5, -4, -3, and -2, cyclophosphamide 14.5 mg/kg for two days on days -6 and -5, 200 cGy total body irradiation (TBI) on day -1, busulfan IV once daily for two days on days -4 and -3, and HSCT on day 0. The busulfan dose will be based on pharmacokinetic levels from the test dose or real time PKs and will be targeted to an AUC of 3600-4800 (Micro)Molmin/L (52-65 mgh/L) (3.2 mg/kg IV per day will be the default dose).

For Post-Transplant GVHD Prophylaxis:

Post-transplant GVHD prophylaxis in all groups will consist of cyclophosphamide 50 mg/kg IV once daily for 2 days on days +3 and +4, along with mycophenolate mofetil from day +5 to approximately day +35 and sirolimus from day +5 to approximately day +180.

Condition Immunodeficiency, Hematopoietic Stem Cell Transplantation
Treatment busulfan, Fludarabine, Sirolimus, Mycophenolate Mofetil (MMF), Cyclophosphamide (CY), allogeneic HSCT, Total Body Irradiation (TBI), Busulfan Test dose, Post-Transplant Cyclophosphamide (PTCY)
Clinical Study IdentifierNCT05027945
SponsorNational Cancer Institute (NCI)
Last Modified on21 October 2022


Yes No Not Sure

Inclusion Criteria

Non-disease related
Age >= 18-year-old and <= 75-year-old
Availability of an 8/8 or 7/8 HLA-matched related or unrelated donor, or a haploidentical related donor
Karnofsky performance status of >= 40%
Adequate end-organ function, defined as follow
Left ventricular ejection fraction > 35%, preferably by 2-D echocardiogram (ECHO) obtained within 60 days prior to treatment initiation
Creatinine <= 2.0 mg/dl and creatinine clearance >= 30 ml/min
Serum conjugated bilirubin < 3.0 mg/dl; serum ALT and AST <= 5 times upper limit of normal
Pulmonary function tests: FEV1 and DLCO >30%
Ability of subject to understand and the willingness to sign a written informed consent document
As therapeutic agents used in this trial may be harmful to a fetus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at the study entry and for at least one-year post-allo HCT. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately
Willingness to remain in the NIH hospital or, if discharged, live within 2 hours drive from the NIH, for a minimum of 100 days after transplant or longer, if there are complications. If outpatient in the first 100 days after transplant, participant must commit to having an adult caregiver with them at all times
Disease related
Somatic mutation in UBA1 performed by a CLIA or CAP certified laboratory. NOTE: Participants without a mutation or unknown mutation status may be eligible if they have a clinical history that is characteristic of an individual with VEXAS syndrome including two or more of a-e below
Inflammatory clinical phenotype for VEXAS syndrome with at least one VEXAS disease manifestation below
constitutional symptoms including fevers, fatigue, and weight loss
cutaneous symptoms of VEXAS including biopsy proven neutrophilic dermatosis, cutaneous vasculitis, periorbital inflammation
pulmonary symptoms of VEXAS with pulmonary infiltrates, pleural effusion
musculoskeletal or cartilaginous involvement including inflammatory arthritis, ear chondritis, and nasal chondritis
inflammatory disease in other major organ systems including cardiac, gastrointestinal, ocular, etc
Presence of cytopenia defined as at least one of the following: i. Absolute neutrophil count <=1000/ L
ii. platelet count <= 75,000/ L or platelet transfusion dependence (at least 4 platelet
transfusions in the 8 weeks prior to study entry
iii. hemoglobin <= 10.0g/dL or red cell transfusion-dependence (at least 4 units of PRBCs
in the 8 weeks prior to treatment initiation) or meeting criteria for myeloid neoplasm (MN)
by WHO criteria
Participants who have failed standard medical management (requiring >= 0.5mg/kg per day of
prednisone for the above listed inflammatory condition or intolerance or refractory to use
of corticosteroids and/or steroid sparing medications as well as biological response
modifiers over the last 6 months), or when no standard medical treatment is available

Exclusion Criteria

HCT Comorbidity Index >= 5
Participants with multiple myeloma. Note: participants with monoclonal gammopathy of
unknown significance will not be excluded)
Participants who are receiving any other investigational agents within the last 30
days before treatment initiation
HIV-positive patients are ineligible because these patients are at increased risk of
lethal infections when treated with marrow-suppressive therapy
History of allergic reactions attributed to compounds of similar chemical or biologic
composition to agents (steroids, cyclophosphamide, busulfan, sirolimus, MMF, G-CSF)
used in the study
Pregnant women are excluded from this study because the study agents have the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with the study agents, breastfeeding should be discontinued if the mother is
treated with the study agents
Uncontrolled intercurrent illness or social situations (as determined by a licensed
master social worker) that would limit compliance with study requirements
Presence of active uncontrolled infections that in the opinion of the PI would make it
unsafe to proceed with transplantation
Active psychiatric disorder which is deemed by the PI to have significant risk of
compromising compliance with the transplant protocol
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note