Ruxolitinib for Eosinophilia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
Approved in 2 Jurisdictions
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.
12345Is 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.
36789How 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.
2471011Eligibility 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.
+16 more
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.
+19 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (ruxolitinib)Experimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stanford Cancer Institute Palo AltoPalo Alto, CA
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Who Is Running the Clinical Trial?
Stanford UniversityLead Sponsor
Jason Robert GotlibLead Sponsor
William ShomaliLead Sponsor
Incyte CorporationIndustry Sponsor
References
JAK inhibition for CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome. [2023]Alternatives are urgently needed in patients with CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome (L-HES) requiring high-level steroids or who are unresponsive and/or intolerant to conventional alternative therapies. We report five L-HES patients (44-66 years) with cutaneous involvement (n = 5) and persistent eosinophilia (n = 3) despite conventional therapies, who successfully received JAK inhibitors (tofacitinib n = 1, ruxolitinib n = 4). JAKi led to complete clinical remission in the first 3 months in all (with prednisone withdrawal in four). Absolute eosinophil counts normalized in cases receiving ruxolitinib, while reduction was partial under tofacitinib. After switch from tofacitinib to ruxolitinib, complete clinical response persisted despite prednisone withdrawal. The clone size remained stable in all patients. After 3-13 months of follow-up, no adverse event was reported. Prospective clinical trials are warranted to examine the use of JAKi in L-HES.
Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. [2021]Ruxolitinib is an oral Janus-activated kinase 1 (JAK1)/JAK2 inhibitor approved for the treatment of patients with myelofibrosis based on the results of two randomized clinical trials. However, discordant indications were provided by regulatory agencies and scientific societies for selecting the most appropriate candidates to this drug. The European LeukemiaNet and the Italian Society of Hematology shared the aim of building evidence-based recommendations for the use of ruxolitinib according to the GRADE methodology. Eighteen patient-intervention-comparator-outcome profiles were listed, each of them comparing ruxolitinib to other therapies with the aim of improving one of the three clinical outcomes: (a) splenomegaly, (b) disease-related symptoms, and (c) survival. Ruxolitinib was strongly recommended for improving symptomatic or severe (>15 cm below the costal margin) splenomegaly in patients with an International Prognostic Scoring System (IPSS)/dynamic IPSS risk intermediate 2 or high. Ruxolitinib was also strongly recommended for improving systemic symptoms in patients with an MPN10 score >44, refractory severe itching, unintended weight loss not attributable to other causes or unexplained fever. Because of weak evidence, the panel does not recommend ruxolitinib therapy for improving survival. Also, the recommendations given above do not necessarily apply to patients who are candidates for allogeneic stem cell transplant.
Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. [2022]Ruxolitinib is a potent Janus kinase (JAK)1/JAK2 inhibitor that has demonstrated rapid reductions in splenomegaly and marked improvement in disease-related symptoms and quality of life in patients with myelofibrosis (MF). The present analysis reports the 3-year follow-up (median, 151 weeks) of the efficacy and safety of Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II (the COMFORT-II Trial), comparing ruxolitinib with the best available therapy (BAT) in 219 patients with intermediate-2 and high-risk MF. In the ruxolitinib arm, with continued therapy, spleen volume reductions of ≥35% by magnetic resonance imaging (equivalent to approximately 50% reduction by palpation) were sustained for at least 144 weeks, with the probability of 50% (95% confidence interval [CI], 36-63) among patients achieving such degree of response. At the time of this analysis, 45% of the patients randomized to ruxolitinib remained on treatment. Ruxolitinib continues to be well tolerated. Anemia and thrombocytopenia were the main toxicities, but they were generally manageable, improved over time, and rarely led to treatment discontinuation (1% and 3.6% of patients, respectively). No single nonhematologic adverse event led to definitive ruxolitinib discontinuation in more than 1 patient. Additionally, patients randomized to ruxolitinib showed longer overall survival than those randomized to BAT (hazard ratio, 0.48; 95% CI, 0.28-0.85; log-rank test, P = .009).
Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review. [2021]Ruxolitinib is a selective Janus kinase inhibitor (JAKI) 1/2 approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). These patients may be at risk for developing opportunistic infections. We assessed the number of patients that developed typical (Mycobacterium tuberculosis [MTB]) and atypical mycobacterial infections (AMI) while on treatment with ruxolitinib by utilizing the United States Food and Drug Administration (FDA) adverse events reporting system (FAERS).
Fedratinib: a pharmacotherapeutic option for JAK-inhibitor naïve and exposed patients with myelofibrosis. [2022]Ruxolitinib is the most commonly used JAK-inhibitor (JAKi) for the management of symptoms related to splenomegaly and cytokine-mediated inflammation in patients with myelofibrosis (MF), but is limited by variable durability of response with most patients experiencing failure after 2-3 years. Long-term data on other approved JAKi, fedratinib and pacritinib, are not available due to the clinical hold put on pivotal trials for toxicity concerns.
Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. [2023]Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials. Over a decade later, ruxolitinib continues to be the standard of care in higher-risk MF, and dose optimization and management remain crucial for safely maximizing clinical benefits of ruxolitinib. This review summarizes the safety profile of ruxolitinib in patients with MF in the COMFORT trials leading up to approval and in the subsequent JUMP, ROBUST, EXPAND, and REALISE trials; in pooled analyses; and in postmarketing analyses in the 10 years following approval. There is a focus on the occurrence of common hematologic and nonhematologic adverse events, with guidance provided on the management of patients with anemia or thrombocytopenia, including dosing strategies based on findings from the REALISE and EXPAND trials. Finally, to ensure a greater understanding of the safety profile of ruxolitinib, practical considerations are discussed.
Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. [2021]Ruxolitinib is a small molecule JAK-2 inhibitor approved for the treatment of certain myeloproliferative neoplasms. Ruxolitinib-related skin toxicity is extremely rare. We report herein an unusual erythematous skin eruption with necrotic centers involving lower extremities in a patient with primary myelofibrosis treated with ruxolitinib. Awareness of this unusual skin toxicity with ruxolitinib becomes even more important as JAK-2 inhibition might soon find clinical applications in dermatology.
Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib. [2022]Ruxolitinib, a novel inhibitor of Janus kinases 1 and 2, was recently approved for the treatment of myelofibrosis but, recently, attention has been drawn to potential side effects and especially opportunistic infections and virus reactivations. EBV reactivation has not previously been reported to occur in association with Ruxolitinib.
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]Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.
Off-label Studies on the Use of Ruxolitinib in Dermatology. [2021]Ruxolitinib (Jakafi) is a Janus kinase 1 and 2 small molecule inhibitor that the Food and Drug Administration approved for myelofibrosis and polycythemia vera. It has been expanded to off-label treatment for a variety of dermatologic conditions, with several clinical trials ongoing. A review of available studies and cases of off-label uses was performed to guide clinicians seeking evidence on the efficacy of this Janus kinase inhibitor for dermatologic disorders.
Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy. [2022]Ruxolitinib is a novel inhibitor of the Janus kinase (JAK) pathway that has become available for the treatment of myelofibrosis. There are increasing reports of opportunistic infections associated with ruxolitinib therapy. We present a case of Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy. Clinicians should consider the use of pneumocystis prophylaxis when using ruxolitinib.