Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease (CGD) With an Alemtuzumab, Busulfan and TBI-based Conditioning Regimen Combined With Cytokine (IL-6, +/- IFN-gamma) Antagonists

Summary

Background:

Chronic granulomatous disease (CGD) affects the immune system. People with CGD are more likely to get infections. Drugs can help control infections, but these treatments can cause side effects including kidney failure and deafness. Stem cell transplants can cure CGD, but these don t always work.

Objective:

To find out if a different drug treatment can improve the success rates of stem cell transplants in people with CGD.

Eligibility:

People aged 4-65 years with CGD.

Design:

Participants will undergo screening. They will have a physical exam. They will have blood and urine tests and tests of their heart function and breathing. They will have imaging scans. They will have a bone marrow biopsy; a needle will be inserted into their hip to draw a sample of tissue from the bone.

A tube called a catheter will be placed into a vein in the participant s chest. This catheter will remain in place for the transplant and recovery period. Blood for tests can be drawn from the catheter, and medications and the stem cells can be administered through it.

Participants will be in the hospital for either 10 or 21 days to receive 3 or 4 drugs before the transplant. They will get 2 doses of total body radiation on the same day.

Participants will receive donor stem cells through the catheter. They will remain in the hospital for 6 weeks afterward.

Participants will visit the clinic 2 to 3 times per week for 3 months after discharge.

Follow-up visits will continue for 5 years.

Conditions

• Chronic Granulomatous Disease

Interventions

DRUG

Sirolimus

Post transplant drug - Immunosuppressant to prevent donor peripheral blood stem cell rejection and graft versus host disease. This is a well studied drug, and is not under an IND.

DRUG

Cyclophosphamide

Post transplant drug - cyclophosphamide give to prevent graft versus host disease. This is a well studied drug and s not under an IND.

DRUG

Alemtuzumab

Transplant Conditioning Drug - Monoclonal antibody that targets recipient and donor T-cells to prevent graft versus host disease. Not an IND. This is a well-studied drug, and is not under an IND.

DRUG

Busulfan

Transplant Conditioning Drug - Chemotherapy to create space in the patient's bone marrow so that the donor peripheral blood stem cells can repopulate in the patient's bone marrow. This is a well studied drug, and is not under IND.

BIOLOGICAL

Pheripheral blood stem cells

Donor peripheral blood stem cells either matched unrelated donors or matched related relative to replace the patient's immune cells with functional immune cells. The peripheral blood stem cells are not regulated by the FDA.

DRUG

Emapalumab-Izsg

Transplant conditioning drug for High Risk Group only - An interferon gamma blocking antibody used to prevent inflammation/engraftment syndrome post HSC transplant.

DRUG

Tociluzumab

Transplant Conditioning Drug - An interleukin-6 (IL-6) receptor antagonist used to decrease Chronic Granulomatous Disease (CGD) inflammation during the HSC transplant process.

DRUG

Total Body Irradiation

Transplant Conditioning - Total Body Irradiation (300 cGy in fractionated doses) to create space n the subject's bone marrow so that the donor peripheral blood stem cells can repopulate in the subject's bone marrow.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Elizabeth M Kang, M.D. · National Institute of Allergy and Infectious Diseases (NIAID)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

4 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-07-08

Primary Completion

2032-12-31

Completion

2032-12-31

Countries

• United States

Study Locations