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

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

Interventions

DRUG

Mycophenolate mofetil (MMF)

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

DRUG

Tacrolimus

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.

DRUG

Busulfan

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

RADIATION

Total Body Irradiation (TBI)

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

DRUG

Fludarabine

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

DRUG

Cyclophosphamide (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

DRUG

Post-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

PROCEDURE

Allogeneic HSCT

stem cell transplant on day 0

DRUG

Busulfan test dose

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

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Bhavisha A Patel, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-23

Primary Completion

2026-07-01

Completion

2026-07-01

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations