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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ustekinumab (also known as Stelara) to determine if it can prevent graft-versus-host disease, a condition where donor cells attack a patient's body after a blood cell transplant. The goal is to assist individuals needing a transplant due to blood cancers or similar disorders. The trial includes two groups: one receives ustekinumab, and the other receives a placebo (a substance with no active drug) for comparison. Suitable candidates have a blood cancer requiring a transplant, a donor match, and stable organ function. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Research shows that ustekinumab is usually well-tolerated by patients. In earlier studies, patients who took ustekinumab lived longer and experienced less severe graft-versus-host disease (GVHD), a condition where transplanted cells attack the body. These studies also suggest that ustekinumab can safely delay the onset of acute GVHD. Although every treatment carries some risks, the evidence supports ustekinumab as a promising option for managing the immune response in transplant patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for preventing graft-versus-host disease (GVHD) in blood cancer patients after a hematopoietic cell transplant (HCT) rely on immunosuppressants like cyclosporine or methotrexate. However, Ustekinumab is unique because it targets specific proteins involved in immune response, such as interleukin-12 and interleukin-23, rather than broadly suppressing the immune system. Researchers are excited about Ustekinumab because it offers a more targeted approach, potentially reducing the risk of severe GVHD without the extensive side effects typical of broader immunosuppressants. Additionally, the treatment's dual delivery method, starting with an intravenous infusion followed by subcutaneous injections, may offer sustained protection against GVHD.

What evidence suggests that ustekinumab might be an effective treatment for preventing acute graft-versus-host disease?

Research shows that ustekinumab, which participants in this trial may receive, may help prevent acute graft-versus-host disease (GVHD) in patients after a stem cell transplant. Studies have found that patients using ustekinumab experienced less moderate to severe GVHD compared to those who received a placebo, another treatment arm in this trial. Ustekinumab targets certain proteins in the immune system that cause inflammation, reducing the risk of the transplanted cells attacking the body. Early findings suggest it can effectively control the immune response, leading to better outcomes for patients. Overall, these studies indicate that ustekinumab shows promise in preventing complications after a transplant. ^{1 2 3 6 7}

Who Is on the Research Team?

Stephanie Lee, MD, MPH

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

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

Signed informed consent

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

My vital organs are functioning well.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04572815

Ustekinumab for the Prevention of Acute Graft-versus-Host ... This phase II trial studies how well ustekinumab works in preventing acute graft-versus-host disease after unrelated donor hematopoietic cell transplant.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-02617

Ustekinumab for the Prevention of Acute Graft-versus-Host ... This phase II trial studies how well ustekinumab works in preventing acute graft-versus-host disease after unrelated donor hematopoietic cell transplant.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8662938/

Translational Clinical Strategies for the Prevention of ... Graft versus host disease (GVHD) is the major non-relapse cause of morbidity and mortality occurring after allogenic hematopoietic stem cell ...

4. researchgate.net researchgate.net/figure/Comparison-of-clinical-outcomes-for-ustekinumab-versus-placebo-treated-subjects-A_fig4_321829201

Comparison of clinical outcomes for ustekinumab versus ... Comparison of clinical outcomes for ustekinumab versus placebo-treated subjects. (A) Cumulative incidence of grade II-IV acute graft-versus-host disease ...

5. withpower.com withpower.com/trial/phase-3-hematologic-diseases-4-2021-d22dd

Ustekinumab for Preventing Graft-versus-Host Disease in ... This trial studies how well ustekinumab works in preventing complications in patients receiving unrelated donor transplants. Ustekinumab helps control the ...

6. grantome.com grantome.com/grant/NIH/R01-FD006836-01

Ustekinumab for Graft versus Host Disease Prevention ... In an initial proof of concept trial clinical trial, we demonstrated that IL-12/23p40 neutralization with the agent ustekinumab safely prolonged time to acute ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5830373/

In vivo IL-12/IL-23p40 neutralization blocks Th1/Th17 ... Overall survival and National Institute of Health moderate/severe chronic GvHD-free, relapse-free survival were significantly improved among ustekinumab-treated ...