A Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome
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|ClinicalTrials.gov Identifier: NCT02400463|
Recruitment Status : Completed
First Posted : March 27, 2015
Results First Posted : November 18, 2020
Last Update Posted : January 25, 2021
|Condition or disease||Intervention/treatment||Phase|
|Hemophagocytic Syndrome (HPS)||Drug: Ruxolitinib||Phase 2|
Hemophagocytic Syndrome (HPS) is a disorder characterized by pathological activation of the immune system resulting in a systemic disorder characterized by excessive cytokine production and macrophage activation, culminating in cytopenias and evidence of hemophagocytosis on tissue specimens. The disorder can be sporadic or familial due to one of several mutations and is primarily seen in the pediatric population, with a reported incidence of 1 case per 3000 admissions. The actual incidence in adults is unknown and can be rarely sporadic, or secondary to viral infections, malignancy, or autoimmune disease.
HPS is a universally fatal disease if untreated. In adults, the median survival has been reported to be less than 2 months if diagnosis and treatment is delayed. Adult patients are treated with pediatric protocols with early institution of etoposide and steroids and consolidation with allogeneic stem cell transplant in appropriately selected patients if a familial form is identified. Other treatment strategies have been attempted, including rituximab, infliximab, entaracept, tocilizumab, and alemtuzumab. These anecdotal reports highlight the therapeutic potential of cytokine-targeted therapies in this disorder.
This is a pilot study to determine the efficacy of Ruxolitinib in secondary hemophagocytic syndrome. The primary objective is to assess the efficacy of ruxolitinib 15 mg PO twice daily in patients with HPS. The primary endpoint is overall survival at two months.
Patients will receive Ruxolitinib at 15 mg twice daily orally either on an empty stomach or with food for 4 weeks (28 days) in a 4 week (28 day) cycle. Ruxolitinib will be administered in continuous 28-day cycles.
In the absence of treatment delays or cessation due to adverse events, treatment may continue indefinitely or until one of the following criteria applies:
- Disease progression.
- Intercurrent illness that prevents further administration of treatment.
- The investigator considers it, for safety reasons, to be in the best interest of the patient.
- Unacceptable adverse events such as any toxicity or other issue that causes a delay of study drug administration by more than 4 weeks.
- General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
- Patient decision to withdraw from treatment (partial consent) or from the study (full consent.
Patients will be followed for toxicity for 30 days after treatment has been discontinued or until death, whichever occurs first.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome|
|Actual Study Start Date :||February 5, 2016|
|Actual Primary Completion Date :||October 10, 2019|
|Actual Study Completion Date :||January 7, 2020|
Ruxolitinib 15 mg by mouth twice daily.
For patients unable to ingest tablets, ruxolitinib suspended in water may be administered through a nasogastric (NG) or percutaneous endoscopy gastrostomy (PEG) tube.
- Overall Survival at 2 Months [ Time Frame: 2 Months ]Number of Patients Alive at 2 Months after the first administration of ruxolitinib.
- Percentage of Patients With a Response to Treatment With Ruxolitinib [ Time Frame: 2 Months ]Complete response is defined as complete normalization of all quantifiable symptoms and laboratory abnormalities. A partial response is defined as at least a 25% improvement in two or more quantifiable symptoms/laboratory markers.
- Duration of Response [ Time Frame: Up to 3 years (Due to funding and other constraints, participant follow-up was discontinued in 2020. Thus, not all participants were followed for a full three years.) ]Duration will be calculated from the date of the determination of partial response or better until the date of progression, death, or additional non-protocol therapy.
- Progression Free Survival Time [ Time Frame: Up to 3 years (Due to funding and other constraints, participant follow-up was discontinued in 2020. Thus, not all participants were followed for a full three years.) ]Progressive Disease is defined as at least a 50% worsening in two or more quantifiable laboratory markers. Calculated from the first administration of ruxolitinib until the date of progression or death.
- Regimen Related Toxicities [ Time Frame: Up to 30 days after last treatment administration ]Incidence and grade of adverse events (AEs) unlikely, possibly or probably related to treatment (tx) with ruxolitinib. Graded per Common Terminology Criteria for Adverse Events (CTCAE) v.4. Grade refers to the severity of the AE, from mild (grade 1) to life-threatening (grade 4).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02400463
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Ryan Wilcox, M.D.||Int Med-Hematology/Oncology - Faculty and Staff|