Ruxolitinib for Eosinophilia

Overseen By Tiffany Nguyen

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Interferon, Imatinib, Antibodies, Hydroxyurea

Disqualifiers: Life-threatening complications, Myeloid neoplasm, Reactive hypereosinophilia, Invasive malignancy, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of ruxolitinib for individuals with certain eosinophilic disorders. These conditions involve the overproduction of eosinophils, a type of white blood cell that can damage organs. The trial seeks participants with high eosinophil counts for at least three months and symptoms or organ issues related to this condition. If previous treatments like corticosteroids have been ineffective or problematic, this trial may be suitable. Participants will take ruxolitinib orally in cycles, provided they do not experience severe side effects or disease progression. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as hydroxyurea within 7 days of starting the study and other specific therapies for eosinophilic disorders within 28 days. If you are on corticosteroids, you must be on a stable dose for at least 28 days before starting the trial.

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

Research has shown that ruxolitinib is generally well-tolerated. For instance, studies on ruxolitinib cream for skin conditions found no new safety concerns. Common side effects were mild, such as cold symptoms and diarrhea, affecting about 1% or more of patients.

For those taking ruxolitinib orally, there is a risk of serious infections that could require hospitalization, but this risk is known and monitored. Overall, the safety of ruxolitinib is well-documented from its use in treating other conditions, which may provide some reassurance about its safety for new uses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ruxolitinib is unique because it targets the JAK-STAT signaling pathway, which plays a crucial role in cell growth and immune function. Unlike existing treatments for eosinophilia that primarily focus on reducing eosinophil levels through corticosteroids or other immunosuppressants, ruxolitinib offers a more targeted approach by inhibiting specific enzymes involved in the overproduction of eosinophils. Researchers are excited about this treatment because it has the potential to provide more effective management of eosinophilia with possibly fewer side effects, offering a new ray of hope for patients who have not responded well to conventional therapies.

What evidence suggests that ruxolitinib might be an effective treatment for eosinophilia?

Research has shown that ruxolitinib, the treatment under study in this trial, can lower eosinophil levels in people with eosinophilic disorders. Eosinophils are a type of white blood cell. In a previous study, 30% of participants experienced a significant decrease in their eosinophil count after three months of treatment. This suggests that ruxolitinib may help manage symptoms of conditions like hypereosinophilic syndrome or primary eosinophilic disorders by reducing eosinophil levels. The evidence from these studies strongly supports ruxolitinib's potential effectiveness in treating these conditions. ^{4 6 7 8 9}

Who Is on the Research Team?

William Shomali, MD

Principal Investigator

Stanford Cancer Institute Palo Alto

Are You a Good Fit for This Trial?

This trial is for patients with hypereosinophilic syndrome or primary eosinophilic disorders, including those newly-diagnosed, on corticosteroids, or with relapsed/refractory disease. Participants must have symptoms of organ damage or enlargement and an absolute eosinophil count >= 1,500/mm^3 (or >= 500/mm^3 in certain conditions). They should be able to consent and have a performance status <= 3. Exclusions include life-threatening complications from the disease, recent serious infections, low platelet counts, prior JAK inhibitor therapy like ruxolitinib.

Inclusion Criteria

- Has as at least 2 readings with an absolute eosinophil count >= 1,500/mm^3 in the preceding 3 months prior to starting ruxolitinib (one reading must be during the screening period).

- Willing and able to review and execute informed consent (legally-authorized consent acceptable).

My cancer has specific genetic changes involving the JAK2 gene.

Exclusion Criteria

I am currently on antibiotics for a serious infection.

- Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 4 x upper limit of normal (ULN) or direct bilirubin > 4 x ULN (if considered to be unrelated to the underlying eosinophilic disorder).

I have not taken hydroxyurea in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ruxolitinib PO BID on days 1-28. Treatment repeats for up to 6 cycles (28 days each) in the absence of disease progression or unacceptable toxicity.

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The trial is testing Ruxolitinib's effectiveness for treating hypereosinophilic syndrome or primary eosinophilic disorders. It's a phase II study which means they're looking at how well it works and its safety in people who fit the criteria.

How Is the Trial Designed?

Group I: Treatment (ruxolitinib) Experimental Treatment 1 Intervention

Patients receive ruxolitinib PO BID on days 1-28. Treatment repeats for up to 6 cycles (28 days each) in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Jason Robert Gotlib

Lead Sponsor

Trials

5

Recruited

50+

William Shomali

Lead Sponsor

Trials

1

Recruited

10+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

Patients treated with ruxolitinib, a JAK inhibitor for myelofibrosis and polycythemia vera, have a significantly increased risk of developing Mycobacterium tuberculosis (MTB) and atypical mycobacterial infections (AMI), with reporting odds ratios of 9.2 and 8.3, respectively.

Out of the reported cases, 13.2% of patients with MTB and 34.8% with AMI died, highlighting the importance of screening for latent MTB before starting ruxolitinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review. Anand, K., Burns, EA., Ensor, J., et al.[2021]

Ruxolitinib, a new treatment for myelofibrosis, has been linked to an increased risk of opportunistic infections, including Pneumocystis jiroveci pneumonitis.

Given this risk, it is recommended that clinicians consider prophylactic measures against Pneumocystis infections for patients undergoing ruxolitinib therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy. Lee, SC., Feenstra, J., Georghiou, PR.[2022]

Ruxolitinib is strongly recommended for patients with myelofibrosis to improve severe splenomegaly and systemic symptoms, particularly in those with specific risk scores and symptoms like severe itching or unexplained weight loss.

However, there is weak evidence supporting the use of ruxolitinib for improving survival, and these recommendations do not apply to patients eligible for allogeneic stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. Marchetti, M., Barosi, G., Cervantes, F., et al.[2021]

Ruxolitinib, a treatment for myelofibrosis, has been associated with a case of EBV reactivation leading to a severe lymphoproliferative disorder in a 57-year-old female patient, highlighting a potential risk of opportunistic infections.

This case emphasizes the need for close monitoring of patients on Ruxolitinib for signs of viral reactivations and opportunistic infections, as they may pose serious health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib. Pálmason, R., Lindén, O., Richter, J.[2022]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, has been the standard treatment for intermediate or high-risk myelofibrosis (MF) since its FDA approval in 2011, demonstrating significant efficacy in improving patient outcomes based on data from the phase 3 COMFORT trials.

The review highlights the importance of dose optimization and management of common side effects, such as anemia and thrombocytopenia, to maximize the safety and clinical benefits of ruxolitinib, supported by findings from subsequent trials like JUMP, ROBUST, EXPAND, and REALISE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. Verstovsek, S., Mesa, RA., Livingston, RA., et al.[2023]

In a study of five patients with CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome (L-HES), treatment with JAK inhibitors (ruxolitinib and tofacitinib) resulted in complete clinical remission within three months for all patients, allowing for prednisone withdrawal in four of them.

No adverse events were reported during 3-13 months of follow-up, suggesting that JAK inhibitors may be a safe and effective alternative for patients with L-HES who are unresponsive to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibition for CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome. Faguer, S., Groh, M., Vergez, F., et al.[2023]

Ruxolitinib, a JAK-2 inhibitor used for treating myeloproliferative neoplasms, is generally associated with very rare skin toxicity, but an unusual case of erythematous skin eruption with necrotic centers was observed in a patient with primary myelofibrosis.

This case highlights the need for increased awareness of potential skin side effects from ruxolitinib, especially as JAK-2 inhibitors may be used more widely in dermatological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. Dasanu, CA.[2021]

In a 3-year follow-up of the COMFORT-II Trial involving 219 patients with myelofibrosis, ruxolitinib demonstrated sustained reductions in spleen size and improved quality of life, with 45% of patients remaining on treatment after 3 years.

Ruxolitinib was well tolerated, with manageable side effects like anemia and thrombocytopenia, and it was associated with longer overall survival compared to the best available therapy, indicating its efficacy and safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Cervantes, F., Vannucchi, AM., Kiladjian, JJ., et al.[2022]

Ruxolitinib, a Janus kinase inhibitor approved for myelofibrosis and polycythemia vera, shows promising efficacy in treating dermatologic conditions like atopic dermatitis, psoriasis, and vitiligo, based on data from clinical trials.

The evidence for ruxolitinib's effectiveness in alopecia areata is mixed, varying between topical and oral formulations, indicating the need for further research to clarify its role in treating various skin disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label Studies on the Use of Ruxolitinib in Dermatology. Tegtmeyer, K., Ravi, M., Zhao, J., et al.[2021]

In a phase 2 trial involving 51 patients with myelofibrosis who were intolerant to ruxolitinib, 43.2% of those treated with the novel JAK inhibitor jaktinib showed a significant reduction in spleen volume after 24 weeks.

Jaktinib also improved symptoms related to myelofibrosis, with 61.8% of patients experiencing a notable decrease in total symptom scores, although it was associated with some serious adverse events, including anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. Zhang, Y., Zhou, H., Duan, M., et al.[2023]

Ruxolitinib is commonly used for managing myelofibrosis symptoms, but many patients experience treatment failure after 2-3 years, highlighting the need for alternative therapies like fedratinib.

Fedratinib has shown efficacy in reducing spleen volume and symptoms in patients with myelofibrosis, and ongoing trials are focused on understanding its long-term effects and managing potential gastrointestinal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fedratinib: a pharmacotherapeutic option for JAK-inhibitor naïve and exposed patients with myelofibrosis. England, JT., Gupta, V.[2022]

Citations

1. jacionline.org jacionline.org/article/S0091-6749(23)01712-8/fulltext

A pilot phase 2 study of ruxolitinib for the treatment ... The primary endpoint was a 30% decrease in absolute eosinophil count (AEC) at 3 months. Participants were eligible to continue ruxolitinib for up to 8 years if ...

2. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-results-phase-3-clinical-trials-evaluating

Incyte Announces Results of Phase 3 Clinical Trials ... As a result, significantly more patients who applied ruxolitinib cream 1.5% versus vehicle control achieved overall treatment success (11.9% vs ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11974361/

Off‐Label Use of Topical Ruxolitinib in Dermatology Part A showed efficacy of 1.5% ruxolitinib cream with a SALT50 (≥ 50% improvement from baseline in SALT) achieved by 50% of patients at week 24.

4. fda.gov fda.gov/media/154307/download

NDA 215309 Ruxolitinib cream OPZELURA is indicated for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1081120622020488

Safety, pharmacokinetics, and efficacy of ruxolitinib cream ... Ruxolitinib cream was well tolerated, with 4 patients (5.6%) experiencing treatment-related adverse events (all grades 1/2).

6. investor.incyte.com investor.incyte.com/news-releases/news-release-details/update-fda-review-ruxolitinib-cream-opzelurar-children-ages-2-11

Update on FDA Review of Ruxolitinib Cream (Opzelura® ... The overall safety profile of Opzelura in the TRuE-AD3 trial was consistent with previous data, and no new safety signals were observed. No serious ...

7. opzelurahcp.com opzelurahcp.com/atopic-dermatitis/skin-clearance-results

Skin Clearance Results | Atopic Dermatitis - Opzelura HCP Patients taking OPZELURA experienced a reduction to 1.4% mean total affected BSA by Week 52 vs. a reduction to 1.7% for those taking the vehicle-to-OPZELURA.

8. fda.gov fda.gov/media/187199/download

Pediatric Postmarketing Pharmacovigilance Review No new safety signals were observed in pediatric patients in this trial. The safety and effectiveness of ruxolitinib in combination with ...

9. incytedermreprints.com incytedermreprints.com/Papp2

Long-term safety and disease control with ruxolitinib cream in ... Patients treated with oral Janus kinase inhibitors for inflammatory conditions are at risk for developing serious infections that may lead to hospitalization ...