Stem Cell Transplant + Cyclophosphamide for Chronic Granulomatous Disease

Not currently recruiting at 1 trial location

Overseen By Elizabeth M Kang, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Disqualifiers: ECOG status, Organ failure, Psychiatric disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination approach to treat chronic granulomatous disease (CGD), a condition where white blood cells struggle to fight infections. The researchers aim to replace faulty cells with healthy donor cells, using drugs like cyclophosphamide (a chemotherapy drug) to reduce complications such as graft versus host disease (GvHD), where donor cells attack the patient's body. The trial seeks individuals with CGD who have experienced significant health issues due to the disease, such as ongoing inflammation or infections despite treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment approach.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that carefully controlling the dose of busulfan in stem cell transplants for chronic granulomatous disease (CGD) can lead to better outcomes. This precision reduces risks during the transplant. Studies have found that cyclophosphamide, another drug used in this treatment, is generally well tolerated, with manageable side effects even for older patients. It has been successfully used to help prevent graft-versus-host disease (GvHD), where the donor's cells attack the recipient's body. Peripheral blood stem cells play a crucial role in this transplant process. They have been effectively used to cure CGD, with patients experiencing good long-term health and growth. Various studies have shown that these treatments are safe, with careful dosing and monitoring significantly reducing potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using stem cell transplants with cyclophosphamide for chronic granulomatous disease because this approach offers a potential cure rather than just symptom management. While most current treatments involve antibiotics and antifungals to control infections, this combination aims to rebuild the immune system using peripheral blood stem cells. Cyclophosphamide helps to suppress the existing immune system, allowing the new stem cells to take hold and function effectively, which is a significant leap forward compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for chronic granulomatous disease?

Research has shown that stem cell transplants can potentially cure chronic granulomatous disease (CGD). This trial involves a single treatment arm where participants receive a combination of stem cell transplants with drugs like busulfan and cyclophosphamide. These drugs help the body accept the new stem cells and reduce the risk of complications, such as graft versus host disease (GvHD), where the donor's cells attack the recipient's body. Early results suggest that this method can strengthen the immune system in people with CGD. ^{6 7 8 9 10}

Who Is on the Research Team?

Elizabeth M Kang, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for people aged 4-65 with Chronic Granulomatous Disease (CGD) who have serious complications from it or low enzyme levels. They need a matched stem cell donor, must be HIV negative, and able to stay near NIH post-transplant with a companion. Participants of childbearing potential must use contraception.

Inclusion Criteria

Must provide a durable power of attorney for health care decisions to an appropriate adult relative or guardian in accordance to NIH -200 NIH Durable Power of Attorney for Health Care Decision Making.

If of child-bearing potential, must agree to consistently use contraception from one month prior to, and throughout, study participation, and for 3 months post-study. Acceptable forms of contraception are: Contraceptive pills or patch, Norplant , Depo-Provera , or other FDA-approved contraceptive method Male partner has previously undergone a vasectomy. Male participants will be advised to consistently use contraception throughout study participation and for 3 months post-transplant.

Must be HIV negative

Exclusion Criteria

I need help with my daily activities due to my health condition.

My CRP levels were over 100 but are now under 100 after treatment.

I have seizures that are not controlled by medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Participants receive alemtuzumab, targeted busulfan, and TBI, followed by a donor graft and post-transplant cyclophosphamide

6-8 weeks

Post-Transplant Monitoring

Participants are monitored for engraftment rates, GvHD, and immune reconstitution

1 year

Follow-up

Participants are monitored for long-term outcomes including event-free survival and overall survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Busulfan
• Cyclophosphamide
• Peripheral blood stem cells
• Sirolimus

Trial Overview The study tests high dose stem cell transplantation using drugs like Alemtuzumab, Busulfan, Sirolimus, Cyclophosphamide and Total Body Irradiation in CGD patients to replace faulty immune cells and reduce GvHD risk.

How Is the Trial Designed?

Group I: 1 Active Control 6 Interventions

There is only one treatment arm for this study

Busulfan is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Malignant lymphoma
• Bone marrow transplantation conditioning

Approved in European Union as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Canada as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Japan as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

A patient with chronic granulomatous disease (CGD) successfully underwent hematopoietic stem cell transplantation (HSCT) using a targeted busulfan and fludarabine conditioning regimen, which minimized toxicity and improved outcomes.

The conditioning involved precise dosing of busulfan and fludarabine, leading to successful engraftment without severe transplantation-related complications, suggesting this approach may enhance HSCT safety and efficacy for CGD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted busulfan and fludarabine-based conditioning for bone marrow transplantation in chronic granulomatous disease. Ju, HY., Kang, HJ., Hong, CR., et al.[2020]

In a study of 69 patients undergoing allogeneic hematopoietic stem cell transplantation with busulfan and cyclophosphamide (Bu/Cy), the three-year overall survival rate was 62%, indicating that this treatment regimen is relatively safe and effective over the long term.

The study found that using body size measures like ideal body weight for dosing busulfan resulted in adequate drug exposure in 73% of patients, suggesting that these measures are important for optimizing treatment, especially in patients with extreme body weights.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Efficacy, Toxicity and Pharmacokinetic Profile of Oral Busulfan in Allogeneic Stem Cell Transplant Patients. Salvaris, R., Salman, S., O'Halloran, S., et al.[2023]

In a study of 42 patients undergoing allogeneic hematopoietic stem cell transplantation, the combination of busulfan and fludarabine (BuFlu) resulted in significantly lower rates of mucositis compared to the traditional busulfan and cyclophosphamide (BuCy) regimen.

Both BuFlu and BuCy showed similar efficacy in terms of engraftment time, relapse risk, event-free survival, and overall survival, suggesting that BuFlu is a viable alternative to BuCy for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine-based myeloablative regimen as pretransplant conditioning therapy in adult acute leukemia/myelodysplastic syndrome: comparison with oral or intravenous busulfan with cyclophosphamide. Lee, JH., Choi, J., Kwon, KA., et al.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

A 22-year-old male with chronic granulomatous disease successfully underwent an allogeneic hematopoietic stem cell transplant, which is notable as he was older than most patients typically treated for this condition.

The patient achieved engraftment by day 13 post-transplant and remains healthy 12 months later, with no serious complications or signs of graft-versus-host disease, indicating the procedure's efficacy and safety in this case.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplant for high-risk adult patients with chronic granulomatous disease: first case report from Iran. Ramzi, M., Rezvani, A., Haghighinejad, H.[2019]

The BUCY regimen, combining busulfan and cyclophosphamide, was found to be safe for autologous hematopoietic stem cell transplantation in 20 patients with multiple myeloma, with no treatment-related mortality within 100 days post-transplant.

Hematopoietic recovery was prompt, with neutrophil and platelet counts returning to normal within 8 to 18 days, and all patients survived the treatment, although the partial remission rate dropped significantly after transplantation, indicating the need for further long-term monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Busulfan Combined with Cyclophosphamide as the Conditioning Regimen in Patients with Multiple Myeloma Treated by Autolo-gous Hematopoietic Stem Cell Transplantation]. Jin, S., Xu, Y., Wang, PF., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02629120

High Dose Peripheral Blood Stem Cell Transplantation ... Chronic granulomatous disease (CGD) affects white blood cell function. Currently, the only curative treatment is bone marrow transplant to replace the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11810765/

Outcomes in hematopoetic cell transplantation in the setting of ... HCT or gene therapy, with appropriate antifungal therapy, are viable therapies for refractory fungal infections in patients with CGD.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02282904

Study Details | NCT02282904 | Haploidentical Transplant ... We propose using a subablative conditioning regimen followed by post-transplant cyclophosphamide for patients with CGD who do not have an HLA matched donor.

4. withpower.com withpower.com/trial/phase-2-granuloma-11-2015-adb23

Stem Cell Transplant + Cyclophosphamide for Chronic ... A patient with chronic granulomatous disease (CGD) successfully underwent hematopoietic stem cell transplantation (HSCT) using a targeted busulfan and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9728560/

Emerging approaches to improve allogeneic hematopoietic ... A prospective multi-institutional study of alternative donor allogeneic HCT in patients with FA using low-dose busulfan, cyclophosphamide, fludarabine, rabbit ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01338675

Study Details | NCT01338675 | Targeted Busulfan, ... In this study the investigators plan to use optimal busulfan dose through pharmacokinetic study in stem cell transplantation of CGD patients.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5177714/

Targeted busulfan and fludarabine-based conditioning for ... Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12389012/

Once-Daily Versus Four-Times-Daily Intravenous Busulfan ... Secondary outcomes included time to primary hematopoietic engraftment within 60 days—neutrophil engraftment was defined as the first of three ...

9. astctjournal.org astctjournal.org/article/S1083-8791(09)00690-9/pdf

Successful Half-Dose Busulfan/Full- ... uCB leads to higher donor- chimerism levels and enzymes which is suggested to have a positive impact on the long term outcomes. ... ADULT CHRONIC GRANULOMATOUS ...

10. nature.com nature.com/articles/s41409-024-02389-x

Outcomes in hematopoetic cell transplantation in the ... We present patient characteristics, microbiological data, and outcomes ... Outcome of chronic granulomatous disease—conventional treatment vs stem ...