NCT05027945 A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Subjects With VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) Syndrome
| NCT ID | NCT05027945 |
| Status | Recruiting |
| Phase | Phase 2 |
| Sponsor | National Cancer Institute (NCI) |
| Condition | Immunodeficiency |
| Study Type | INTERVENTIONAL |
| Enrollment | 54 participants |
| Start Date | 2023-02-23 |
| Primary Completion | 2026-07-01 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.
This trial targets 54 participants in total. It began in 2023-02-23 with a primary completion date of 2026-07-01.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
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....
Eligibility Criteria
* 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: 1. Left ventricular ejection fraction \> 35%, preferably by 2-D echocardiogram (ECHO) obtained within 60 days prior to treatment initiation. 2. Creatinine \<= 2.0 mg/dl and creatinine clearance \>= 30 ml/min; 3. 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: 1. constitutional symptoms including fevers, fatigue, and weight loss 2. cutaneous symptoms of VEXAS including biopsy proven neutrophilic dermatosis, cutaneous vasculitis, periorbital inflammation 3. pulmonary symptoms of VEXAS with pulmonary infiltrates, pleural effusion 4. musculoskeletal or cartilaginous involvement including inflammatory arthritis, ear chondritis, and nasal chondritis 5. 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/ microliter ii. platelet count \<= 75,000/microliter 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 updated 2022 WHO criteria or 2022 International Consensus Classification (ICC) of myeloid neoplasms and acute leukemia OR: -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. Note: Comorbidities that are specifically addressed in the inclusion criteria will not be included in the calculation of HCT-CI score. * 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.
Contact & Investigator
Bhavisha A Patel, M.D.
PRINCIPAL INVESTIGATOR
National Cancer Institute (NCI)
Frequently Asked Questions
Who can join the NCT05027945 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 75 Years, studying Immunodeficiency. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05027945 trial and what does that mean for participants?
Phase 2 trials evaluate whether the treatment shows signs of effectiveness while continuing to monitor safety. More participants are enrolled than in Phase 1 to help refine the treatment protocol.
Is NCT05027945 currently recruiting?
Yes, NCT05027945 is actively recruiting participants. Contact the research team at bhavisha.patel@nih.gov for enrollment information.
Where is the NCT05027945 trial being conducted?
This trial is being conducted at Bethesda, United States.
Who is sponsoring the NCT05027945 clinical trial?
NCT05027945 is sponsored by National Cancer Institute (NCI). The principal investigator is Bhavisha A Patel, M.D. at National Cancer Institute (NCI). The trial plans to enroll 54 participants.