Ustekinumab for Preventing Graft-versus-Host Disease in Blood Cancer Patients

Recruiting at 4 trial locations

Overseen By Stephanie J. Lee

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Anti-thymocyte globulin

Disqualifiers: Active infection, HIV, Hepatitis, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 24 weeks

116 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how well ustekinumab works in preventing complications in patients receiving unrelated donor transplants. Ustekinumab helps control the immune system to stop it from attacking the body's tissues. The goal is to protect patients from complications after their transplant. Ustekinumab has been used in the treatment of autoimmune conditions such as psoriasis, psoriatic arthritis, and Crohn's disease.

Will I have to stop taking my current medications?

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 Ustekinumab generally safe for humans?

Ustekinumab, also known as Stelara, has been used to treat conditions like Crohn's disease, psoriasis, and psoriatic arthritis. It is generally well tolerated, with serious infections and major side effects being rare in clinical trials. ^{1 2 3 4 5}

How is the drug Ustekinumab unique for preventing graft-versus-host disease?

Ustekinumab is unique because it targets specific proteins involved in the immune response, which may help prevent graft-versus-host disease by reducing inflammation differently than traditional immunosuppressive drugs. This approach is novel compared to other treatments that primarily focus on broadly suppressing the immune system. ^{6 7 8 9 10}

Research Team

Stephanie Lee, MD, MPH

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults aged 18-70 with blood cancers or disorders needing a stem cell transplant from an unrelated donor. Participants must have good heart, lung, and liver function, a specific level of physical fitness (Karnofsky Score ≥ 70%), and matched donors. Pregnant women, those with prior transplants, certain non-malignant blood disorders, active infections not under control, HIV/hepatitis B/C infections or unwillingness to use birth control are excluded.

Inclusion Criteria

I am between 18 and 70 years old.

Signed informed consent

I need a bone marrow transplant for my blood cancer or disorder.

Exclusion Criteria

My treatment plan involves low-intensity or specific dose chemotherapy.

I have had a transplant from a donor.

I agree to use birth control or not have sex until 15 weeks after the last dose.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Patients receive conditioning therapy followed by hematopoietic cell transplantation (HCT)

1 week

Treatment

Participants receive ustekinumab or placebo intravenously and subcutaneously at specified intervals post-HCT

24 weeks

3 visits (in-person) for SC administration

Follow-up

Participants are monitored for safety, effectiveness, and incidence of GVHD and other outcomes

24 months

Visits at 6, 9, 12, 18, and 24 months post-HCT

Treatment Details

Interventions

• Ustekinumab

Trial Overview The study tests if Ustekinumab can prevent acute graft-versus-host disease after receiving stem cells from an unrelated donor. It compares the effects of Ustekinumab against a placebo in patients undergoing transplantation while monitoring their quality of life through questionnaires.

Participant Groups

Group I: Arm I (ustekinumab) Experimental Treatment 3 Interventions

Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab IV. Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

Group II: Arm II (placebo) Placebo Group 3 Interventions

Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

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

Approved in European Union as Stelara for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Crohn's disease
• Ulcerative colitis

Approved in United States as Stelara for:

• Moderate to severe plaque psoriasis
• Active psoriatic arthritis
• Moderately to severely active Crohn's disease
• Moderately to severely active ulcerative colitis

Approved in Canada as Stelara for:

• Moderate to severe plaque psoriasis
• Active psoriatic arthritis
• Moderately to severely active Crohn's disease
• Moderately to severely active ulcerative colitis

Approved in Japan as Stelara for:

• Plaque psoriasis
• Psoriatic arthritis
• Crohn's disease
• Ulcerative colitis

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Findings from Research

Ustekinumab (STELARA) is effective for treating moderate-to-severe plaque psoriasis in pediatric patients aged 6 to 12, as shown by a phase III study that developed a pharmacokinetic model to predict its behavior in this age group.

The study successfully used data from adult patients to create a model that predicts clinical responses in children, indicating that ustekinumab's efficacy and safety profile can be extrapolated from adults to younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrapolating Pharmacodynamic Effects From Adults to Pediatrics: A Case Study of Ustekinumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis. Zhou, W., Hu, C., Zhu, Y., et al.[2021]

Ustekinumab, an interleukin-12 and -23 antagonist, is primarily used for moderate to severe plaque psoriasis and other inflammatory conditions, but emerging literature suggests it may also be effective for various off-label uses, including other types of psoriasis and hidradenitis suppurativa.

Despite promising findings for these off-label conditions, the review highlights the need for more clinical trials to thoroughly evaluate the safety and efficacy of ustekinumab beyond its approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label uses of ustekinumab. Ye, L., Wu, Z., Li, C., et al.[2023]

Ustekinumab is an effective treatment for adults with moderately to severely active Crohn's disease who have not responded to or are intolerant of other therapies, showing improved clinical response and remission rates in pivotal phase III trials.

The drug has a unique mechanism of action targeting IL-12 and IL-23 cytokines, and it is generally well tolerated, with serious side effects like infections and malignancies being rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. Lamb, YN., Duggan, ST.[2018]

Ustekinumab is an effective treatment for adults with active psoriatic arthritis, showing significant improvement compared to placebo in phase 3 trials, with benefits maintained up to 100 weeks.

The drug has a favorable safety profile, with rare occurrences of serious infections or major cardiovascular events, making it a valuable option for patients who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ustekinumab: a review of its use in psoriatic arthritis. McKeage, K.[2021]

In a study of 36 adults with Crohn's disease, 61% responded to ustekinumab treatment after one year, but no distinct gene expression signature was found to predict response, indicating that more research is needed to identify reliable biomarkers.

Among nonresponders, an increased inflammatory response was observed, with 68 genes linked to cytokine activity and chemokine receptor binding, suggesting that these pathways may play a role in treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. Granot, M., Braun, T., Efroni, G., et al.[2023]

Tacrolimus has been found to be effective in preventing graft-versus-host disease (GVHD) in patients undergoing allogeneic bone marrow transplants, highlighting its potential as a critical intervention in this high-risk population.

Further research is necessary to refine dosage schedules and establish therapeutic ranges to ensure both efficacy and safety in the use of tacrolimus for GVHD prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus: an alternative for graft-versus-host disease prevention. Lee, TJ., Kennedy, LA.[2017]

Graft-versus-host disease (GVHD) is a major complication following allogeneic bone marrow transplantation, making it crucial to balance immune responses to prevent GVHD while preserving the beneficial graft-versus-leukemia effect.

Current treatments involve various immunosuppressive drugs that target different stages of GVHD, suggesting that a combination therapy approach may be more effective than relying on a single agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunosuppressive drugs in the prevention and treatment of GVHD after allogenic bone marrow transplantation]. Basić-Jukić, N., Labar, B.[2009]

Acute graft-versus-host disease (GVHD) affects about 50% of transplant patients and is a major cause of mortality, highlighting the importance of effective prevention strategies like T-cell depletion.

Modern treatments for GVHD include JAK/STAT pathway inhibitors, which are now standard for second-line therapy and are being explored for early intervention based on patient risk factors, although options beyond second-line treatment remain limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Graft-versus-Host Disease: An Update on New Treatment Options. Patel, DA., Crain, M., Pusic, I., et al.[2023]

In a study of 141 patients undergoing hematopoietic stem cell transplantation, treatment with tacrolimus plus sirolimus (Tac/Sir) did not increase the incidence or severity of severe oral mucositis compared to cyclosporine plus methotrexate (CsA/Mtx).

Both treatment groups experienced similar healing patterns for oral mucositis, with peak severity occurring on day 10 and returning to baseline by day 24, indicating that Tac/Sir is a safe alternative for graft-versus-host disease prophylaxis without worsening oral mucositis outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral mucositis after tacrolimus/sirolimus or cyclosporine/methotrexate as graft-versus-host disease prophylaxis. Garming Legert, K., Ringdén, O., Remberger, M., et al.[2022]

Basiliximab is shown to be a safe and effective treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD), with an overall response rate of 79.4% in a study involving 940 patients across 36 hospitals in China.

Using basiliximab as monotherapy resulted in similar efficacy to combined therapies but with lower infection rates, highlighting the importance of treatment strategy in managing SR-aGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis. Mo, XD., Hong, SD., Zhao, YL., et al.[2022]

References

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

Extrapolating Pharmacodynamic Effects From Adults to Pediatrics: A Case Study of Ustekinumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis. [2021]

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

Off-label uses of ustekinumab. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ustekinumab: A Review in Moderate to Severe Crohn's Disease. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Ustekinumab: a review of its use in psoriatic arthritis. [2021]

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

Baseline peripheral blood mononuclear cell (PBMC) transcriptomics before ustekinumab treatment is linked with Crohn Disease clinical response at 1 year. [2023]

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

Tacrolimus: an alternative for graft-versus-host disease prevention. [2017]

7. Croatia pubmed.ncbi.nlm.nih.gov

[Immunosuppressive drugs in the prevention and treatment of GVHD after allogenic bone marrow transplantation]. [2009]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Acute Graft-versus-Host Disease: An Update on New Treatment Options. [2023]

9. Denmark pubmed.ncbi.nlm.nih.gov

Oral mucositis after tacrolimus/sirolimus or cyclosporine/methotrexate as graft-versus-host disease prophylaxis. [2022]

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

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis. [2022]