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

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well ruxolitinib works in treating patients with hypereosinophilic syndrome or primary eosinophilic disorders.

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.

What data supports the effectiveness of the drug Ruxolitinib for treating eosinophilia?

Ruxolitinib has shown effectiveness in treating conditions with high eosinophil counts, like lymphocytic-variant hypereosinophilic syndrome, where it led to complete clinical remission and normalized eosinophil counts in patients. Additionally, it is effective in reducing symptoms and improving quality of life in myelofibrosis, a different condition, suggesting its potential in managing eosinophilia. ^{1 2 3 4 5}

Is ruxolitinib generally safe for humans?

Ruxolitinib has been used for over a decade to treat myelofibrosis, and while it is generally well tolerated, some patients may experience side effects like anemia (low red blood cell count) and thrombocytopenia (low platelet count), which are usually manageable. Rarely, it can cause skin reactions or increase the risk of infections, so monitoring by a healthcare provider is important. ^{3 6 7 8 9}

How is the drug Ruxolitinib unique for treating eosinophilia?

Ruxolitinib is unique because it is a Janus kinase (JAK) inhibitor, which means it works by blocking specific enzymes involved in the immune response, potentially offering a novel approach for conditions like eosinophilia where standard treatments may not exist. ^{2 4 7 10 11}

Research Team

William Shomali, MD

Principal Investigator

Stanford Cancer Institute Palo Alto

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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]

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]

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]

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]

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, 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]

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]

References

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

JAK inhibition for CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. [2021]

3. United States 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. [2022]

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

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Fedratinib: a pharmacotherapeutic option for JAK-inhibitor naïve and exposed patients with myelofibrosis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib. [2022]

9. United States 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. [2023]

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

Off-label Studies on the Use of Ruxolitinib in Dermatology. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy. [2022]