RecruitingPhase 2NCT05027945

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


Sponsor

National Cancer Institute (NCI)

Enrollment

54 participants

Start Date

Feb 23, 2023

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 18 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This study is testing whether a bone marrow transplant (allogeneic hematopoietic stem cell transplantation) can cure or significantly improve VEXAS syndrome — a rare, recently discovered inflammatory disease caused by a mutation in the UBA1 gene. VEXAS can cause severe inflammation, blood problems, and is often resistant to standard treatments. You may be eligible if: - You are 18 to 75 years old - You have confirmed VEXAS syndrome (UBA1 mutation or characteristic clinical features) - You have a matched or haploidentical donor available - You have significant disease manifestations (inflammation, low blood counts, transfusion dependence, or disease not responding to medications) - Your heart, kidney, liver, and lung function meet minimum requirements You may NOT be eligible if: - You have multiple myeloma (low-risk smoldering myeloma is not excluded) - You are HIV positive - You are pregnant or breastfeeding - You have an uncontrolled active infection - You have a significant psychiatric disorder that would interfere with the transplant process - You have a very high comorbidity index (HCT-CI score of 5 or more) Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDUREAllogeneic HSCT

stem cell transplant on day 0

DRUGBusulfan test dose

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

DRUGMycophenolate mofetil (MMF)

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

DRUGTacrolimus

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.

DRUGBusulfan

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

RADIATIONTotal Body Irradiation (TBI)

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

DRUGFludarabine

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

DRUGCyclophosphamide (CY)

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

DRUGPost-Transplant Cyclophosphamide (PTCY)

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


Locations(1)

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

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NCT05027945


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