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A Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome

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ClinicalTrials.gov Identifier: NCT02400463
Recruitment Status : Recruiting
First Posted : March 27, 2015
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hemophagocytic Syndrome (HPS) Drug: Ruxolitinib Phase 2

Detailed Description:

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.
  • Death.

Patients will be followed for toxicity for 30 days after treatment has been discontinued or until death, whichever occurs first.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome
Study Start Date : September 2015
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ruxolitinib

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.

Drug: Ruxolitinib



Primary Outcome Measures :
  1. Number of Patients Alive at 2 Months [ Time Frame: 2 Months ]

Secondary Outcome Measures :
  1. 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.

  2. Duration of Response [ Time Frame: Up to 2 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. For patients lost to follow-up, duration will be censored at the time of last clinical assessment.

  3. Progression Free Survival Time [ Time Frame: 2 Months ]
    Progressive Disease is defined as at least a 50% worsening in two or more quantifiable laboratory markers.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients, or their legally authorized representative, must voluntarily provide written IRB-approved informed consent.
  • Males and females, 18 years of age or older at the time of enrollment.
  • Patients must meet the diagnostic criteria for HPS (at least 5 of the following): fever, splenomegaly, cytopenia involving ≥2 cell lines (Hemoglobin <9 g/dL; platelets <100,000/μL; absolute neutrophil count <1000/μL), hypertriglyceridemia or hypofibrinogenemia, tissue demonstration of hemophagocytosis, low or absent NK (Natural Killer) cell activity, serum ferritin ≥3000 ug/L, soluble IL-2 receptor (CD25) >2400 U/mL.
  • In the investigator's opinion, the patient has the ability to participate fully in the study, and comply with all its requirements.

Exclusion Criteria:

  • CNS (Central Nervous System) involvement
  • Malabsorption
  • Known secondary HPS (Hemophagocytic Syndrome) that is otherwise treatable (e.g. non-Hodgkin's lymphoma).
  • Pregnant or lactating female: all females of child-bearing potential must have a negative serum pregnancy test within 7 days of treatment; lactating females must discontinue breast feeding.
  • Estimated creatinine clearance <15mL/min
  • Has received any prior systemic therapy, excluding corticosteroids, within 7 days (or 5 half-lives) of treatment.
  • No active malignancy at the time of enrollment, except nonmelanoma skin cancers or carcinoma in situ. Patients with a prior history of malignancy are eligible if their malignancy has been definitely treated or is in remission and does not require ongoing adjuvant or cancer-directed therapies.
  • Active hepatitis B or hepatitis C or known HIV infection
  • Known (and biopsy-confirmed) liver cirrhosis; or, a reported history of liver cirrhosis with a Model for End-stage Liver Disease (MELD) score >20.

Information from the National Library of Medicine

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


Contacts
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Contact: Ryan Wilcox, M.D. 734/615-1482 rywilcox@umich.edu

Locations
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United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Ryan Wilcox, M.D.    734-615-1482    rywilcox@umich.edu   
Principal Investigator: Ryan Wilcox, M.D.         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Ryan Wilcox, M.D. Int Med-Hematology/Oncology - Faculty and Staff

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT02400463     History of Changes
Other Study ID Numbers: UMCC 2014.112
HUM00092921 ( Other Identifier: University of Michigan )
First Posted: March 27, 2015    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Lymphohistiocytosis, Hemophagocytic
Syndrome
Disease
Pathologic Processes
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases