50 Participants Needed

Stem Cell Transplant + Drug Therapy for Chronic Granulomatous Disease

CK
EM
SM
Overseen BySandra M Maxwell, R.N.
Age: Any Age
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

What data supports the effectiveness of the treatment for Chronic Granulomatous Disease?

Research shows that allogeneic hematopoietic stem cell transplantation, which includes drugs like alemtuzumab and busulfan, is a curative treatment for Chronic Granulomatous Disease. Studies have reported successful outcomes with high survival rates and low incidence of infections in patients who underwent this treatment.12345

What safety data exists for the drugs used in stem cell transplant and drug therapy for chronic granulomatous disease?

The safety of cyclophosphamide, one of the drugs used in this treatment, has been studied in other conditions. It is known to cause side effects like bone marrow suppression, which can lead to a low white blood cell count, increasing the risk of infections. Careful monitoring and dosage adjustments are important to manage these risks.678910

How is the Stem Cell Transplant + Drug Therapy for Chronic Granulomatous Disease unique?

This treatment is unique because it combines stem cell transplantation with a specific set of drugs, including Alemtuzumab, Busulfan, Cyclophosphamide, and Emapalumab-Izsg, along with Total Body Irradiation, to potentially improve outcomes for patients with Chronic Granulomatous Disease. This combination aims to enhance the effectiveness of the transplant and reduce the risk of complications compared to traditional conditioning regimens.1251112

What is the purpose of this trial?

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.

Research Team

EM

Elizabeth M Kang, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

This trial is for people aged 4-65 with Chronic Granulomatous Disease (CGD) who have complications from the disease or a specific level of oxidase production. They must not be HIV positive, pregnant, or breastfeeding and should agree to use contraception. Participants need an HLA-matched stem cell donor and must stay close to the NIH post-transplant.

Inclusion Criteria

Stated willingness to comply with all study procedures and is available for protocol visits for the duration of the study when possible.
I have been diagnosed with Chronic Granulomatous Disease (CGD).
I have a donor match for my transplant.
See 10 more

Exclusion Criteria

I do not have an active TB infection.
Ejection fraction of less than 30% by echocardiography.
My lung function tests show severe limitations.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Conditioning and Transplantation

Participants receive conditioning regimen including Alemtuzumab, Busulfan, and TBI, followed by donor stem cell transplantation

10-21 days
In-hospital stay

Post-Transplant Recovery

Participants remain in the hospital for recovery and monitoring after receiving donor stem cells

6 weeks
In-hospital stay

Initial Follow-up

Participants visit the clinic for monitoring and assessment of engraftment and infection rates

3 months
2-3 visits per week (in-person)

Long-term Follow-up

Participants are monitored for overall survival, engraftment stability, and absence of GvHD

5 years
Periodic visits

Treatment Details

Interventions

  • Alemtuzumab
  • Busulfan
  • Cyclophosphamide
  • Emapalumab-Izsg
  • Tociluzumab
  • Total Body Irradiation
Trial Overview The study tests if a combination of drugs including Busulfan, Sirolimus, Cyclophosphamide, Alemtuzumab plus cytokine antagonists Emapalumab-Izsg and Tocilizumab can improve stem cell transplant success in CGD patients. It includes pre-transplant medication, total body irradiation, and follow-up for five years.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm 2 / Group 2 High Risk.Experimental Treatment7 Interventions
Group 2 (High risk group will receive tociluzumab at day -24, a repeat dose at day -19, Alemtuzumab at day -9,-8,-7,-6,-5; Busulfan at day -4 and -3, Emapalumab at Day -1, matched donor PBSC infusion, and post transplant cyclophosphamide at Day +3 and +4
Group II: Arm 1 / Group 1 Standard RiskActive Control7 Interventions
Group 1 (Standard group) will receive tociluzumab at Day -10, Alemtuzumab on Day -9,-8,-7,-6,-5; Busulfan on Day -4, and -3, TBI, matched donor PBSC infusion, and Post transplant Cyclophosphamide.

Alemtuzumab is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Campath for:
  • Chronic lymphocytic leukemia
  • Multiple sclerosis
🇪🇺
Approved in European Union as Lemtrada for:
  • Multiple sclerosis
🇪🇺
Approved in European Union as Campath for:
  • Chronic lymphocytic leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials
3,361
Recruited
5,516,000+

Findings from Research

A single-center study involving four patients with chronic granulomatous disease (CGD) showed that a reduced-intensity conditioning regimen (RIC) using alemtuzumab and other agents led to early immune recovery and a low rate of infections post-transplant.
The study reported a 75% disease-free survival rate at a median follow-up of five years, suggesting that this RIC approach is a viable alternative for CGD patients who cannot tolerate traditional busulfan-based conditioning.
A single-center experience using alemtuzumab, fludarabine, melphalan, and thiotepa as conditioning for transplantation in pediatric patients with chronic granulomatous disease.Bhatt, ST., Schulz, G., Hente, M., et al.[2020]
In a study involving 10 patients with chronic granulomatous disease, a reduced intensity conditioning regimen for allogeneic hematopoietic stem-cell transplantation showed promising results, with 8 out of 10 patients alive and well after a median follow-up of at least 2 years.
The use of donor lymphocyte infusion in three patients who developed mixed donor chimerism suggests a potential strategy to enhance treatment outcomes in this patient population.
An Experience of Donor Lymphocyte Infusion after Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease.Rostami, T., Kiumarsi, A.[2020]
Chronic granulomatous disease (CGD) is a rare immunodeficiency that leads to difficulty in fighting certain infections and causes inflammation, but new antibiotics and antifungals are improving survival rates into adulthood.
Allogeneic hematopoietic stem cell transplantation is currently the only proven cure for CGD, while gene-replacement therapy is still experimental but has shown some promise in treating severe infections in patients without suitable donors.
Modern management of chronic granulomatous disease.Seger, RA.[2017]

References

A single-center experience using alemtuzumab, fludarabine, melphalan, and thiotepa as conditioning for transplantation in pediatric patients with chronic granulomatous disease. [2020]
An Experience of Donor Lymphocyte Infusion after Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease. [2020]
Modern management of chronic granulomatous disease. [2017]
Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome. [2023]
Allogeneic hematopoietic stem cell transplant for high-risk adult patients with chronic granulomatous disease: first case report from Iran. [2019]
Complications associated with immunosuppressive therapy and their management. [2013]
Rituximab as Induction Therapy in Eosinophilic Granulomatosis with Polyangiitis Refractory to Conventional Immunosuppressive Treatment: A 36-Month Follow-Up Analysis. [2018]
Methotrexate plus leflunomide for the treatment of relapsingWegener's granulomatosis. A retrospective uncontrolled study. [2018]
Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations. [2022]
Two cases of refractory eosinophilic granulomatosis with polyangiitis wherein mepolizumab was effective against pulmonary and ear lesions. [2021]
Health related quality of life and emotional health in children with chronic granulomatous disease: a comparison of those managed conservatively with those that have undergone haematopoietic stem cell transplant. [2021]
12.Korea (South)pubmed.ncbi.nlm.nih.gov
Targeted busulfan and fludarabine-based conditioning for bone marrow transplantation in chronic granulomatous disease. [2020]
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