Hemophagocytic Syndrome (HPS)Phase 2NCT02400463
A Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome
A Phase 2 study testing Ruxolitinib in people with Hemophagocytic Syndrome (HPS), run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemophagocytic Syndrome (HPS)
- What is being tested?
- Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Feb 2016to 7 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome
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.
Read the 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.
- Conditions
- Hemophagocytic Syndrome (HPS)
- Being tested
- Ruxolitinib
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib | Experimental | 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. Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival at 2 Months
Number of Patients Alive at 2 Months after the first administration of ruxolitinib.
Measured: 2 Months
Secondary outcomes (4)
Percentage of Patients With a Response to Treatment With Ruxolitinib
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.
Measured: 2 Months
Duration of Response
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.
Measured: 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.)
Progression Free Survival Time
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.
Measured: 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.)
Regimen Related Toxicities
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).
Measured: Up to 30 days after last treatment administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2015 (estimated)
- Study start5 Feb 2016
- Primary completion10 Oct 2019
- Study completion7 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophagocytic Syndrome (HPS)Studies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ryan Wilcox, M.D., Principal investigator, Int Med-Hematology/Oncology - Faculty and Staff
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02400463
- Sponsor's protocol ID
- UMCC 2014.112
- Other IDs
- HUM00092921
- Status last verified
- Jan 2021
- First submitted
- 22 Jan 2015
- Last updated
- 25 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ahmed A, Merrill SA, Alsawah F, Bockenstedt P, Campagnaro E, Devata S, Gitlin SD, Kaminski M, Cusick A, Phillips T, Sood S, Talpaz M, Quiery A, Boonstra PS, Wilcox RA. Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: an open-label, single-centre, pilot trial. Lancet Haematol. 2019 Dec;6(12):e630-e637. doi: 10.1016/S2352-3026(19)30156-5. Epub 2019 Sep 16.
PubMed 31537486
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Ruxolitinib in Secondary Hemophagocytic Syndrome
- ClinicalTrials.gov ID
- NCT02400463
- Acronym / sponsor ID
- UMCC 2014.112
- Conditions
- Hemophagocytic Syndrome (HPS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- 5 Feb 2016 (actual)
- Primary completion
- 10 Oct 2019 (actual)
- Study completion
- 7 Jan 2020 (actual)
- First posted
- 27 Mar 2015 (estimated)
- Results
- Posted 18 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib | Experimental | Drug: RuxolitinibRuxolitinib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ruxolitinib | Drug | Ruxolitinib |
Primary outcome
Overall Survival at 2 Months
Time frame: 2 Months
Number of Patients Alive at 2 Months after the first administration of ruxolitinib.
4 secondary outcomes
Percentage of Patients With a Response to Treatment With Ruxolitinib
Time frame: 2 Months
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.)
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.)
Regimen Related Toxicities
Time frame: Up to 30 days after last treatment administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31537486Ahmed A, Merrill SA, Alsawah F, Bockenstedt P, Campagnaro E, Devata S, Gitlin SD, Kaminski M, Cusick A, Phillips T, Sood S, Talpaz M, Quiery A, Boonstra PS, Wilcox RA. Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: an open-label, single-centre, pilot trial. Lancet Haematol. 2019 Dec;6(12):e630-e637. doi: 10.1016/S2352-3026(19)30156-5. Epub 2019 Sep 16.
- The Lancet Haematology, VOLUME 6, ISSUE 12, E630-E637, DECEMBER 01, 2019Link provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryan Wilcox, M.D. principal investigator
Int Med-Hematology/Oncology - Faculty and Staff
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib in people with Hemophagocytic Syndrome (HPS), run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival at 2 Months (time frame: 2 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02400463, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2021; AzTrials last refreshed its copy on 8 Nov 2026.