Budesonide for Engraftment Syndrome After Stem Cell Transplant

Overseen By shatha farhan

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Henry Ford Health System

Disqualifiers: Other trials, Non-hematologic malignancies

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 days

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether budesonide, a corticosteroid medication, can reduce engraftment fever, a common fever after stem cell transplants, in individuals who have undergone a stem cell transplant for blood cancers. Participants will either take budesonide or receive no additional treatment to determine budesonide's effectiveness. Individuals with blood cancers scheduled for a stem cell transplant and meeting specific transplant program criteria may qualify. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for this trial?

The trial information 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.

Is there any evidence suggesting that budesonide is likely to be safe for humans?

Research has shown that budesonide is generally safe for people. Studies have found that adding budesonide to certain treatment plans can help prevent serious gut problems without causing major side effects. For example, one study found that using budesonide with other medications effectively and safely prevented severe gut issues after transplants.

Budesonide is also used to treat other conditions, indicating that many patients tolerate it well. However, like any treatment, it can have side effects, so monitoring for any unusual symptoms is important. Overall, the evidence supports the safety of budesonide in similar situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Budesonide is unique because it is a corticosteroid that is delivered directly to the gut, which could effectively target the inflammation seen in engraftment syndrome after a stem cell transplant. Traditional treatments for engraftment syndrome often involve systemic steroids, which can have widespread side effects. By focusing the treatment on the gut, Budesonide may minimize these side effects while still addressing the core issue. Researchers are excited about this potential because it could offer a more targeted and safer option for managing this challenging condition.

What evidence suggests that budesonide might be an effective treatment for engraftment syndrome?

Research has shown that budesonide, which participants in this trial may receive, can lower the risk of engraftment syndrome (ES), a condition that may occur after a stem cell transplant. One study found that using budesonide as a preventive measure significantly reduced the chances of ES in patients undergoing these transplants. This treatment has produced promising results in improving patients' health without causing serious side effects. Additionally, budesonide has effectively treated other issues related to stem cell transplants, such as stomach problems, by easing symptoms without requiring stronger treatments. Overall, these findings suggest that budesonide could be a helpful option for patients after a stem cell transplant. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 who are set to undergo stem cell transplantation for blood cancers. It's not open to those getting transplants for non-blood cancers or anyone already in another clinical study.

Inclusion Criteria

I am eligible for a stem cell transplant according to the BMT program's criteria.

Exclusion Criteria

I have had a stem cell transplant for a cancer that is not related to blood.

Patients enrolled in investigational clinical trials

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Budesonide prophylaxis starting day 5 after transplant to reduce engraftment fever

10 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide

Trial Overview The trial is testing if budesonide, started on day 5 after a transplant, can prevent engraftment fever in patients receiving their own (autologous) or donor (allogeneic) stem cells.

How Is the Trial Designed?

Group I: Budesonide Experimental Treatment 1 Intervention

Group II: nothing Active Control 1 Intervention

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

Approved in European Union as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Crohn's disease
• Ulcerative colitis
• Microscopic colitis
• Eosinophilic esophagitis
• Primary immunoglobulin A nephropathy

Approved in United States as Entocort EC for:

• Crohn's disease
• Ulcerative colitis
• Primary immunoglobulin A nephropathy
• Eosinophilic esophagitis

Approved in Canada as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis

Who Is Running the Clinical Trial?

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Published Research Related to This Trial

Engraftment syndrome (ES) occurred in 19.2% of pediatric patients undergoing autologous peripheral blood progenitor cell transplantation, leading to significant complications such as hypoxia, hepatic dysfunction, and renal insufficiency.

The use of high-dose G-CSF for mobilization was identified as a strong predictor for developing ES, which was associated with a higher transplant-related mortality rate (23% in ES patients vs. 4.76% in non-ES patients), highlighting the need for careful monitoring and management in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engraftment syndrome in children undergoing autologous peripheral blood progenitor cell transplantation. Madero, L., Vicent, MG., Sevilla, J., et al.[2004]

In a study of 71 patients, budesonide-MMX demonstrated a significantly better safety profile compared to methylprednisolone, with only 1.9% experiencing glucocorticoid-related adverse events compared to 47.4% in the methylprednisolone group.

The efficacy of budesonide-MMX was influenced by the CYP3A5 genotype, suggesting that genetic factors may play a role in how well patients respond to this treatment, although further research is needed to explore this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible genetical predictors of efficacy and safety of budesonide-MMX in patients with mild-to-moderate ulcerative colitis, and safety comparison with methylprednisolone. Resál, T., Mangó, K., Bacsur, P., et al.[2023]

Corticosteroid prophylaxis significantly reduced the incidence of engraftment syndrome (ES) following autologous stem cell transplantation (ASCT), with only 10% of patients in the corticosteroid group experiencing ES compared to 40% in the control group (p < 0.001).

While corticosteroids did not significantly shorten hospitalization duration between the two cohorts, they effectively lowered the risk of ES, suggesting a beneficial role in managing patients post-ASCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic corticosteroid use prevents engraftment syndrome in patients after autologous stem cell transplantation. Betticher, C., Bacher, U., Legros, M., et al.[2021]

In a study of 156 adult patients undergoing autologous stem cell transplantation (ASCT), 29% developed engraftment syndrome (ES), with symptoms like fever, rash, and diarrhea being more common in these patients.

Risk factors for developing ES included a shorter time from diagnosis to ASCT and fewer pretransplant treatment regimens, but early recognition and steroid treatment have improved survival outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postautologous stem cell transplantation engraftment syndrome: Improved treatment and outcomes. Liu, Z., Zhang, S., Horn, B., et al.[2021]

In a study of 32 adult patients undergoing syngeneic hematopoietic stem cell transplantation (HSCT), 47% developed engraftment syndrome (ES), indicating a significant incidence of this complication in syngeneic HSCT, which had not been previously documented.

Patients with ES showed a trend towards higher nonrelapse mortality (21%) compared to those without ES (0%), suggesting that ES may impact long-term outcomes, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Syngeneic donor hematopoietic stem cell transplantation is associated with high rates of engraftment syndrome. Koreth, J., Biernacki, M., Aldridge, J., et al.[2011]

In a study involving 12 healthy volunteers, the extended-release formulation of budesonide (Uceris®) showed a similar overall exposure to the drug compared to Entocort® EC, as measured by the area under the concentration-time curve (AUC).

However, Uceris® had a delayed pharmacokinetic profile, with a longer time to first appearance in plasma and a delayed peak concentration, suggesting it may provide more effective delivery of the medication to the colon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability profile of Uceris MMX extended-release tablets compared with Entocort EC capsules in healthy volunteers. Nicholls, A., Harris-Collazo, R., Huang, M., et al.[2013]

In a study of 16 patients with acute leukemia undergoing allogeneic bone marrow transplantation, 14 achieved complete and sustained engraftment using a preparatory regimen of fractionated total body irradiation and high-dose etoposide.

However, two patients experienced graft rejection, suggesting that etoposide may be less effective than cyclophosphamide in preventing graft rejection, indicating a potential risk when using etoposide as an immunosuppressive agent in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graft rejection and recovery of host-derived hematopoiesis after allogeneic bone marrow transplantation: relation to conditioning with high dose etoposide and total body irradiation. Hara, M., Shinagawa, K., Omoto, E., et al.[2019]

In a study involving 159 adults with moderate-to-severe asthma, budesonide delivered via an inhaler significantly reduced the need for oral glucocorticosteroids (GCSs) by 79-83% compared to only 27% in the placebo group, indicating its efficacy in managing asthma while minimizing systemic steroid use.

Approximately two-thirds of participants using budesonide were able to completely stop oral corticosteroids, and they also experienced improvements in lung function and asthma symptoms, suggesting that budesonide not only spares oral GCSs but also maintains or enhances asthma control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group. Nelson, HS., Bernstein, IL., Fink, J., et al.[2019]

A 56-year-old man with acute myeloid leukemia underwent reduced-intensity cord blood transplantation (RIC-CBT) after failing multiple chemotherapy regimens, and despite complications, he achieved complete remission after treatment.

The administration of low-dose etoposide was effective in resolving hemophagocytic syndrome (HPS), a serious complication that can hinder engraftment, suggesting it may be a safe and effective treatment option in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Successful treatment with low-dose etoposide for hemophagocytic syndrome following reduced-intensity conditioning for cord blood transplantation in a patient with acute myelgenous leukemia]. Tokushige, J., Ueki, T., Sato, K., et al.[2013]

Oral budesonide (Entocort EC) is an effective treatment for mild to moderate Crohn's disease, particularly in the ileum and ascending colon, showing similar efficacy to prednisolone and better results than mesalamine.

Budesonide has a favorable safety profile with fewer systemic side effects compared to prednisolone, although it does not prevent postsurgical relapse and requires monitoring for hepatic dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral budesonide in the management of Crohn's disease. Hofer, KN.[2007]

Budesonide inhalation suspension significantly improves both nighttime and daytime asthma symptoms in children under 4 years and those 4 years and older, based on a retrospective analysis of two randomized studies involving children aged 6 months to 8 years.

The treatment is generally safe, with no significant differences in adverse events between age groups, although a notable effect on hypothalamic-pituitary-adrenal-axis function was observed in younger children at the lowest dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily budesonide inhalation suspension in infants and children or = 4 years of age with persistent asthma. Scott, MB., Ellis, MH., Cruz-Rivera, M., et al.[2019]

Citations

1. cancernursingtoday.com cancernursingtoday.com/post/study-shows-oral-budesonide-is-an-effective-addition-to-ptcy-based-gvhd-prophylaxis

Study Evaluates Adding Oral Budesonide to PTCy-Based ... In looking at other outcomes with this regimen, the rate of non-relapse mortality was 17%, overall survival was 80.9%, progression-free survival ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124101814

Efficacy of Budesonide Monotherapy for Low Grade GI ... Budesonide monotherapy resulted in excellent ORRs without the addition of systemic therapy, sparing patients toxicities associated with systemic treatment.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12483468/

Budesonide, Added to PTCy-Based Regimen, for ... In conclusion, addition of budesonide to PTCy-based GVHD prophylaxis is safe and effective in preventing severe acute GI GVHD with significantly improved GRFS.

4. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(21)00209-3/abstract

Budesonide Prophylaxis Reduces the Risk of Engraftment ... Budesonide prophylaxis significantly reduces the risk of ES in MM patients undergoing AHCT. These promising results suggest the need for a ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39985640/

Incidence of engraftment syndrome with and without ... This study aims to determine if budesonide prophylaxis reduces ES after autologous hematopoietic cell transplantation (auto-HCT) for patients with multiple ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ajh.27581

Budesonide, Added to PTCy‐Based Regimen, for ... In conclusion, addition of budesonide to PTCy-based GVHD prophylaxis is safe and effective in preventing severe acute GI GVHD with significantly ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05405387

Impact of Budesonide on Incidence of ≥ Gr2 Diarrhea in ... The trial will initiate with a safety run-in of 20 pts with a ≥ 5 pts failing to engraft (or having a Grade 4 or higher infection rate) within 18 days as ...

8. astctjournal.org astctjournal.org/article/S2666-6367(25)00824-3/pdf

REMOVED Conclusion: Based on a single-center experience, a shortened course of Defibrotide in patients who achieve CR can be safe without risk of VOD recurrence.

9. researchgate.net researchgate.net/publication/389256029_Incidence_of_engraftment_syndrome_with_and_without_budesonide_prophylaxis_in_patients_with_multiple_myeloma_undergoing_autologous_stem_cell_transplant

Incidence of engraftment syndrome with and without ... This study aims to determine if budesonide prophylaxis reduces ES after autologous hematopoietic cell transplantation (auto-HCT) for patients ...