Stem Cell Transplant + Cyclophosphamide for Chronic Granulomatous Disease

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

45 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Stem Cell Transplant + Cyclophosphamide for Chronic Granulomatous Disease?

Research shows that hematopoietic stem cell transplantation (HSCT) is a curative treatment for chronic granulomatous disease (CGD), with successful outcomes reported in patients using conditioning regimens that include busulfan and cyclophosphamide. Studies indicate that most patients achieve disease-free survival and good clinical condition after transplant, suggesting the effectiveness of this treatment approach. ^{1 2 3 4 5}

Is the combination of busulfan and cyclophosphamide generally safe for humans?

The combination of busulfan and cyclophosphamide has been used in stem cell transplants for various conditions, and while it can cause side effects like nausea, vomiting, and liver issues, it is generally considered manageable. Serious complications can occur, but the overall safety profile is acceptable with proper medical supervision. ^{6 7 8 9 10}

How is the treatment with stem cell transplant and cyclophosphamide unique for chronic granulomatous disease?

This treatment is unique because it combines a stem cell transplant with cyclophosphamide and busulfan, which are used to prepare the body to accept new stem cells, potentially offering a cure for chronic granulomatous disease. Unlike other treatments that may only manage symptoms, this approach aims to correct the underlying immune deficiency by replacing defective cells with healthy ones from a donor. ^{1 3 4 11 12}

What is the purpose of this trial?

Chronic granulomatous disease (CGD) affects white blood cell function. Currently, the only curative treatment is bone marrow transplant to replace the abnormal stem cells with new ones (donor cells) capable of making a normal immune system. Transplant problems include graft versus host disease (GvHD) and graft rejection. With GvHD, donor cells attack the recipient s normal tissue. Researchers want to use preparation drugs and a high cell dose to increase graft success. They want to use 2 immunosuppressive drugs (cyclophosphamide and sirolimus) to lessen the risk of GvHD.

Research Team

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 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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Targeted busulfan and fludarabine-based conditioning for bone marrow transplantation in chronic granulomatous disease. [2020]

2. Singapore pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation in a boy with chronic granulomatous disease. [2018]

3. Turkey pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplant for high-risk adult patients with chronic granulomatous disease: first case report from Iran. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Allogeneic stem cell transplant from HLA-identical sibling for chronic granulomatous disease and review of the literature. [2013]

5. United States 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. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A modified busulfan and cyclophosphamide preparative regimen for allogeneic transplantation in myeloid malignancies. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

Evaluating the Efficacy, Toxicity and Pharmacokinetic Profile of Oral Busulfan in Allogeneic Stem Cell Transplant Patients. [2023]

8. Korea (South) 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. [2021]

9. China 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]. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Toxicity of high-dose busulphan and cyclophosphamide as conditioning therapy for allogeneic bone marrow transplantation in adults with haematological malignancies. [2013]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation as therapy for chronic granulomatous disease--single centre experience. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease. [2021]