Steroid Tapering for Pediatric Graft-versus-Host Disease

Recruiting at 11 trial locations

Overseen By Janna Baez

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: John Levine

Must not be taking: Corticosteroids

Disqualifiers: Uncontrolled infection, Chronic GVHD, others

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

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

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

Compensation: Varies

Number of Visits: 90

Duration: 4 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if children with graft-versus-host disease (GVHD) can safely take lower doses of steroids, specifically prednisone, without losing benefits. Researchers have developed a blood test to predict a child's response to steroids, enabling dose reduction for those likely to respond well. By using fewer steroids, the trial seeks to lower the risk of side effects such as infections and bone damage. It is suitable for children up to age 21 who have just been diagnosed with GVHD and have not yet received systemic steroid treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance for potentially safer steroid use.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking corticosteroids at more than 0.1 mg/kg prednisone (or equivalent) for any reason within 7 days before the onset of acute GVHD, you may not be eligible to participate.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that patients should not have been treated with certain doses of steroids recently. It's best to discuss your current medications with the trial team to see if they affect your eligibility.

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

Research shows that prednisone, a common steroid for treating graft-versus-host disease (GVHD), can cause both short-term and long-term side effects. Short-term effects may include infections, high blood sugar, high blood pressure, muscle weakness, depression, anxiety, and sleep problems. Long-term use can lead to bone damage, cataracts, and stunted growth. Higher doses and longer treatment periods increase these risks.

However, studies have found that lower doses of prednisone can still be effective and might reduce these side effects. Researchers are exploring ways to safely lower prednisone amounts by using a blood test to predict which patients will respond well to treatment. By identifying these patients early, doctors can gradually reduce the steroid dose, potentially minimizing side effects while still effectively managing the disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pediatric graft-versus-host disease (GVHD), which typically involve a one-size-fits-all approach to steroid dosing, this new steroid tapering method personalizes the treatment based on each child's unique biomarker profile and clinical response. Researchers are excited about this approach because it aims to optimize steroid use, potentially reducing side effects and improving outcomes by adjusting doses precisely to the child's needs. This tailored approach could lead to more effective management of GVHD, offering hope for better recovery and quality of life for affected children.

What evidence suggests that this steroid tapering protocol is effective for pediatric GVHD?

Research has shown that low-dose prednisone can be as effective as standard doses for treating acute graft-versus-host disease (GVHD) in children. In this trial, all enrolled patients will start on the same dose of steroids, with adjustments based on biomarkers and clinical response. Studies have found that these lower doses are safe and do not increase the need for additional treatments later. Initial findings suggest that children with low levels of GVHD markers respond well to steroids, indicating they might not require high doses for extended periods. This approach could reduce the risk of side effects like infections and bone damage. Overall, evidence supports using lower doses without losing effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Muna Qayed, MD, MS

Principal Investigator

Children's Healthcare of Atlanta, Emory University School of Medicine

John E Levine

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for children and young adults (0-21 years) with a specific immune reaction called GVHD after bone marrow transplant. They must have certain biomarkers, not been treated with systemic steroids for GVHD before, and be in good physical condition. Pregnant individuals or those with severe liver disease, uncontrolled infections, or serious organ dysfunction cannot participate.

Inclusion Criteria

My condition is diagnosed with Grade 1 GVHD based on biomarkers.

I have been newly diagnosed with GVHD, but it's not just a skin rash or only in my upper GI tract.

I am mostly active and can care for myself.

Exclusion Criteria

My liver is not functioning well, shown by high bilirubin or liver enzyme levels.

I do not have an infection that is getting worse despite treatment.

My cancer is getting worse or not improving, needing a change in my immune therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive steroid treatment with dose adjustments based on biomarker and clinical response over four weeks

4 weeks

Weekly visits for dose adjustment and biomarker assessment

Follow-up

Participants are monitored for safety, effectiveness, and complications such as serious infections and overall survival

12 months

Bi-weekly visits through day 90, then periodic follow-ups

What Are the Treatments Tested in This Trial?

Interventions

• Prednisone

Trial Overview The trial tests if tapering steroid medication quickly can effectively treat GVHD in patients who are likely to respond well based on their biomarker levels. It aims to reduce the duration of high-dose steroid treatment to minimize side effects while monitoring symptoms and quality of life.

How Is the Trial Designed?

Group I: Steroid Taper Experimental Treatment 1 Intervention

All enrolled patients start on the same dose of steroids for treatment of GVHD, blood samples are taken at week 1 and 2 post study start and biomarkers plus clinical response determines how steroid treatment is continued

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

Approved in United States as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in European Union as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in Canada as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Who Is Running the Clinical Trial?

John Levine

Lead Sponsor

Trials

4

Recruited

230+

Published Research Related to This Trial

In a study of 733 transplant patients, initial treatment of acute graft-versus-host disease (GVHD) with low-dose glucocorticoids (1 mg/kg/day) was found to be as effective as standard-dose glucocorticoids (2 mg/kg/day) in terms of overall mortality and disease relapse.

Patients receiving low-dose glucocorticoids experienced reduced risks of invasive fungal infections and shorter hospital stays, indicating that this treatment approach may lead to lower toxicity without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes. Mielcarek, M., Storer, BE., Boeckh, M., et al.[2021]

In a phase III study involving 164 patients with newly diagnosed acute graft-versus-host disease, initial treatment with lower dose prednisone (0.5 mg/kg/day for grade IIa and 1 mg/kg/day for grade IIb or higher) was found to be effective without increasing the need for secondary immunosuppressive therapy in grade IIa patients.

However, for patients with grade IIb or higher manifestations, the lower dose was associated with a significantly higher risk (41% vs. 7%) of requiring additional immunosuppressive treatment, indicating that while lower doses may be safe for some, they may not be sufficient for more severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of lower dose prednisone for initial treatment of acute graft-versus-host disease: a randomized controlled trial. Mielcarek, M., Furlong, T., Storer, BE., et al.[2022]

In a study of 745 patients with chronic graft-versus-host disease (cGVHD), variations in initial treatment approaches, including different doses of prednisone and the use of non-steroid therapies, did not significantly impact failure-free survival, overall survival, or non-relapse mortality.

The findings highlight the need for prospective trials to explore the efficacy of reduced-dose prednisone or prednisone-free treatment strategies, as current practices show considerable heterogeneity without clear outcomes benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial therapy for chronic graft-versus-host disease: analysis of practice variation and failure-free survival. Pidala, J., Onstad, L., Martin, PJ., et al.[2022]

In a study of 30 bone marrow transplant patients with moderate/severe acute graft-versus-host disease (GVHD), a longer tapering schedule of corticosteroids led to faster resolution of GVHD symptoms compared to a shorter taper, with median resolution times of 30 days versus 42 days, respectively.

Both tapering schedules resulted in similar rates of chronic GVHD and survival at 6 months, indicating that while the tapering duration affects the speed of symptom resolution, it does not impact long-term outcomes or steroid-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisone therapy for acute graft-versus-host disease: short- versus long-term treatment. A prospective randomized trial. Hings, IM., Filipovich, AH., Miller, WJ., et al.[2019]

In a study of 196 allogeneic blood and marrow transplant patients, prophylaxis with cyclosporine and prednisone (CYA-PRED) was linked to a significantly higher risk of developing chronic graft-versus-host disease (cGVHD) compared to cyclosporine with methotrexate (CYA-MTX), with a risk ratio of 3.5.

Patients receiving CYA-PRED also had a higher cumulative probability of extensive cGVHD at 2 years, indicating that the choice of GVHD prophylaxis can greatly influence patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylaxis of graft-versus-host disease with cyclosporine-prednisone is associated with increased risk of chronic graft-versus-host disease. Kumar, S., Chen, MG., Gastineau, DA., et al.[2013]

In a randomized trial involving 287 patients with chronic graft-versus-host disease (GVHD), the combination of cyclosporine (CSP) and prednisone did not significantly reduce transplantation-related mortality compared to prednisone alone, with 5-year mortality rates of 17% and 13%, respectively.

However, the combination treatment with CSP and prednisone was associated with a lower incidence of avascular necrosis (13% vs. 22%), suggesting it may help reduce steroid-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone. Koc, S., Leisenring, W., Flowers, ME., et al.[2021]

In a study of 864 patients treated with prednisone for acute graft-versus-host disease (GVHD), the response at day 28 was found to be a strong predictor of 2-year transplantation-related mortality (TRM), making it the optimal early endpoint for therapeutic trials.

Patients who did not respond by day 28 were 2.78 times more likely to experience TRM within 2 years, highlighting the importance of early response assessment in managing GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The best endpoint for acute GVHD treatment trials. MacMillan, ML., DeFor, TE., Weisdorf, DJ.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11235274/

Treatment of steroid-refractory graft versus host disease in ... This Review aims to critically explore the current evidence regarding novel approaches to treat SR-GvHD in pediatric HSCT recipients.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666636722013690

Clinical Features, Treatment, and Outcome of Pediatric ... Our study demonstrates that SR-aGvHD confers a high mortality risk in pediatric HSCT. Older age and use of CB grafts are associated with an unfavorable outcome.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5709112/

Steroid treatment of acute graft-versus-host disease grade I In conclusion, steroid treatment of acute grade I GvHD prevents progression to grade II but not to grade III–IV GvHD, and there is no effect on non-relapse ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7695/528686/Safety-and-Efficacy-of-Low-Dose-Versus-High-Dose

Safety and Efficacy of Low Dose Versus High Dose ... Low-dose prednisone showed similar efficacy to standard-dose for most GVHD outcomes (relapse risk, mortality), with potential benefits on survival.

5. withpower.com withpower.com/trial/phase-3-graft-vs-host-disease-2-2022-f3ebb

Steroid Tapering for Pediatric Graft-versus-Host Disease A phase III study found that lower dose prednisone is effective and safe for acute GVHD without increasing secondary treatment incidence. Another study compared ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05090384

NCT05090384 | Pediatric GVHD Low Risk Steroid Taper Trial The standard treatment for acute graft-vs-host disease (GVHD) is to suppress the activity of the donor immune cells using steroid medications such as prednisone ...

7. haematologica.org haematologica.org/article/view/8291

Steroid treatment of acute graft-versus-host disease grade I Effectiveness and safety of lower dose prednisone for initial treatment of acute graft-versus-host disease: a randomized controlled trial.

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ajh.27592?af=R

Steroid Refractory Acute GVHD: The Hope for a Better ... Steroid-refractory acute graft-versus-host disease (SR-AGVHD) presents a significant barrier to successful outcomes following allogeneic ...