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

NCT05027945 | Recruiting Phase 2 FDA Drug FDA Device

• 2 other identifiers: 10000404000404-C
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Immunodeficiency; Hematopoietic Stem Cell Transplantation

Keywords

Immune Dysregulation; Haploidentical; hematoinflammatory diseases; Myelodysplastic Syndromes; Autoimmune Disorders

Outcome Measures

Primary Outcomes (2)

• Reversal of clinical phenotype of VEXAS

  fraction of subjects who achieve complete clinical response without use of additional glucocorticoid therapy and without steroid-sparing therapy

  +1 and +2 years post HSCT

• Sustained donor engraftment

  defined as neutrophil recovery with ANC = 500/mm\^3 for 3 consecutive days associated with \> 50% T-cell and myeloid cell donor chimerism at day 100 and one year post-HSCT

  day +100 and +1 year post HSCT

Secondary Outcomes (3)

• Safety of allo HSCT

  +1, +2 and +3 years post HSCT

• incidence of grade III-IV acute GVHD and moderate to severe chronic GVHD

  +1 and +2 years post HSCT

• Overall survival and event free survival

  +1, +2 and +3 years post HSCT

Study Arms (2)

Arm A

EXPERIMENTAL

Reduced intensity regimen (Fludarabine, busulfan)+HSCT+GVHD prophylaxis

Procedure: Allogeneic HSCT; Drug: Busulfan test dose; Drug: Mycophenolate mofetil (MMF); Drug: Tacrolimus; Drug: Busulfan; Drug: Fludarabine; Drug: Post-Transplant Cyclophosphamide (PTCY)

Arm B

EXPERIMENTAL

Reduced intensity regimen (Fludarabine, low dose cyclophosphamide, 200cGY TBI, busulfan)+HSCT+GVHD prophylaxis

Procedure: Allogeneic HSCT; Drug: Busulfan test dose; Drug: Mycophenolate mofetil (MMF); Drug: Tacrolimus; Drug: Busulfan; Radiation: Total Body Irradiation (TBI); Drug: Fludarabine; Drug: Cyclophosphamide (CY); Drug: Post-Transplant Cyclophosphamide (PTCY)

Interventions

Allogeneic HSCT PROCEDURE

stem cell transplant on day 0

Arm A; Arm B

Busulfan test dose DRUG

0.8 mg/kg IV over 2 hours. May be skipped if real-time PKs are done during conditioning.

Arm A; Arm B

Mycophenolate mofetil (MMF) DRUG

Mycophenolate mofetil (MMF): 15 mg/kg IV over 2 hours BID starting on day +5 until approximately day +35 (+/-2 days)

Arm A; Arm B

Tacrolimus DRUG

Starting on day +5, start at 0.02 mg/kg IV continuous infusion over 24 hours until day +180 and titrated to trough levels of 5-15 mg/ml.

Arm A; Arm B

Busulfan DRUG

AUC Targeted Dose based on busulfan test dose PKs, IV infusion over 3 hours once daily (3.2 mg/kg IV per day will be the default dose) per the below time frame: For 8/8 Matched Related or Unrelated Donor Busulfan dose will be on days -6, -5, and -4 For 7/8 Matched Related or Unrelated or Haploidentical Donor Busulfan dose will be on days -4 and -3

Arm A; Arm B

Total Body Irradiation (TBI) RADIATION

For 7/8 Matched Related or Unrelated or Haploidentical Donor, 200cGy on day -1

Arm B

Fludarabine DRUG

40 mg/m2 IV over 30 mins daily For 8/8 Matched Related or Unrelated Donor Fludarabine dose will be on days -6, -5, -4, and -3 For 7/8 Matched Related or Unrelated or Haploidentical Donor Fludarabine dose will be on days -6, -5, -4, -3, and -2

Arm A; Arm B

Cyclophosphamide (CY) DRUG

For 7/8 Matched Related or Unrelated or Haploidentical Donor, prior to transplant 14.5 mg/kg IV daily on days -6 and -5

Arm B

Post-Transplant Cyclophosphamide (PTCY) DRUG

Post-Transplant Cyclophosphamide: 50 mg/kg IV daily over 2 hours on days +3 and +4, dosed according to ideal body weight

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, individuals 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 an individual become pregnant or suspect they are 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:

You may not qualify if:

• Participants with multiple myeloma. Note: participants with low risk smoldering multiple myeloma or 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, tacrolimus, MMF, filgrastim or filgrastim biosimilar) used in the study.
• Pregnant individuals 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (2)

• Fiumara M, Campochiaro C, Molteni R. Decoding VEXAS syndrome: emerging insights into pathogenesis and clinical management. Curr Opin Rheumatol. 2026 Jan 1;38(1):45-52. doi: 10.1097/BOR.0000000000001137. Epub 2025 Nov 5.

  PMID: 41175032 DERIVED

• Koster MJ, Samec MJ, Warrington KJ. VEXAS Syndrome-A Review of Pathophysiology, Presentation, and Prognosis. J Clin Rheumatol. 2023 Sep 1;29(6):298-306. doi: 10.1097/RHU.0000000000001905. Epub 2022 Oct 17.

  PMID: 36251488 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Immunologic Deficiency Syndromes; Myelodysplastic Syndromes; Autoimmune Diseases

Interventions

Mycophenolic Acid; Tacrolimus; Busulfan; Whole-Body Irradiation; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Immune System Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Bhavisha A Patel, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bhavisha A Patel, M.D.

CONTACT

(301) 402-3477; bhavisha.patel@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2021
• First Posted: August 31, 2021
• Study Start: February 23, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 8, 2026

Record last verified: 2026-05-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.

Locations

US (1)