AzTrials
AzTrials

Hemophagocytic LymphohistiocytosisPhase 2NCT02007239

Tocilizumab and Hemophagocytic Lymphohistiocytosis (HLH)

A Phase 2 study testing tocilizumab in people with Hemophagocytic Lymphohistiocytosis, run by Children's Hospital of Philadelphia at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This study seeks to determine the efficacy of tocilizumab (TCZ) in patients with hemophagocytic lymphohistiocytosis (HLH) and high cytokine levels (proteins involved in inflammation) in an attempt to decrease the damage caused by these proteins; and secondarily to assess its safety and impact on disease activity. Read more about this study

Who is it for?
Ages 3 months to 25 years
Conditions the study is for
Hemophagocytic Lymphohistiocytosis
What is being tested?
tocilizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Dec 2013to May 2021
Phase
Phase 2
Are there results?
None posted in the registry

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 3 months to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Males or females age 3 months to 25 years.
  • Fulfill the clinical diagnostic criteria for HLH, as defined by the Histiocyte Society (see Table 1). Only patients with de novo HLH are eligible.
  • Evidence of cytokine release syndrome (CRS), as defined by EITHER:
  • Known elevated interferon-γ and interleukin-6 ≥2x ULN, OR ii. If cytokine levels are unknown at the time of study enrollment:
  • Fever of at least 38.5º celsius at minimum of once every 24 hours for at least 48 hours, AND either i. Respiratory insufficiency requiring oxygen supplementation of at least 2 Liter by nasal cannula for at least 12 hours (also including invasive, noninvasive, continuous positive airway pressure or biphasic airway pressure for the purpose of treating respiratory failure), OR ii. Vasoactive infusion for at least 12 hours, including dopamine ≥5mcg/kg/min, dobutamine≥5mcg/kg/min, or any dose of epinephrine, norepinephrine, milrinone, or vasopressin.
  • Patients must be planned to initiate HLH-directed therapy within 24 hours of study enrollment.
  • Girls >= 11 years of age must have a negative urine/serum pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study.
  • Parental/guardian permission (informed consent)

Who cannot join

  • On-going or planned participation in another clinical trial involving HLH-directed treatment
  • Previous administration of any other biologic agent targeted at cytokine blockade within 5 days of enrollment.
  • Renal insufficiency defined by estimated glomerular filtration rate (based on modified Schwartz formula) <50 ml/min, or need for renal replacement therapy.
  • Hepatic dysfunction as defined by serum alanine aminotransferase (ALT)>=10x upper limit of normal (ULN). For the purposes of this study, the ULN for ALT is 45 U/L.
  • HLH that is relapsed, refractory, or considered to be therapy-related, as in the case of T cell-activating therapies.
  • Established prior diagnosis of underlying rheumatologic condition, including juvenile idiopathic arthritis.
Show all 14Show fewer
  • Pregnant or lactating females.
  • Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
  • Suspected gastrointestinal perforation.
  • Known or suspected demyelinating central nervous system disease.
  • Known history of tuberculosis.
  • Transfusion-refractory thrombocytopenia defined as inability to maintain platelet count over 30,000/ul for at least 6 hours with transfusion support.
  • Known active herpetic infection.
  • Inability to start HLH-directed immunochemotherapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Cytokine Blockade With Tocilizumab in Patients With Cytokine Release Syndrome and Hemophagocytic Lymphohistiocytosis

This study seeks to determine the efficacy of tocilizumab (TCZ) in patients with hemophagocytic lymphohistiocytosis (HLH) and high cytokine levels (proteins involved in inflammation) in an attempt to decrease the damage caused by these proteins; and secondarily to assess its safety and impact on disease activity.

Read the detailed description

Subjects with hemophagocytic lymphohistiocytosis (HLH) often have life-threatening complications at the time of diagnosis resulting from excessive inflammation. This excessive inflammation is driven by abnormally high levels of cytokines--proteins involved in inflammation. Standard therapy for HLH does not directly target these cytokines. Tocilizumab is a medicine that blocks one of the cytokines that is elevated in patients with HLH.

This is an open-label single-arm uncontrolled trial with biologic endpoint. This study will use tocilizumab in subjects with HLH and high cytokine levels in an attempt to decrease the damage caused by these proteins. All subjects will receive standard therapy, in addition to tocilizumab. We hypothesize the tocilizumab will decrease levels of certain important cytokines. This may make it easier to treat subjects with HLH overall.

TCZ will be administered as a single dose (8mg/kg) intravenously. Eligible subjects will be inpatients at the Children's Hospital of Philadelphia (CHOP) main campus. 10 subjects with HLH will be enrolled. All subjects will be initiated on standard HLH-directed treatment. Cytokine levels [including serum interferon (IFN-γ) and interleukin (IL-6)] will be monitored, in addition to other laboratory and clinical markers of HLH disease activity.

Being tested
tocilizumab
Keywords
tocilizumab, hemophagocytic lymphohistiocytosis (HLH), cytokine, cytokine release syndrome
Medical subject headings
Lymphohistiocytosis, Hemophagocytic, Cytokine Release Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tocilizumabDrug

    Also called TCZ

    single dose of tocilizumab (8mg/kg intravenously) within 24 hours of administration of standard immunochemotherapy.

Study groups in NCT02007239
Study groupRoleWhat they receive
treatmentExperimentalsingle dose of tocilizumab (8mg/kg intravenously) within 24 hours of administration of standard immunochemotherapy.
Receives: Drug: tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction in serum interferon-gamma levels after tocilizumab (TCZ) administration

    Assess change in interferon gamma levels from the screening visit to the measurements taken within 24-36 hours and at 4-7 days after drug administration.

    Measured: baseline, 24 -36 hours, and 4-7 days after administration of TCZ

Secondary outcomes (4)

  1. Change in other cytokine levels (interleukin-6, interleukin-10, tumor necrosis factor-alpha, etc.)

    Cytokine levels [IL-1, IL-2, sIL-2r, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, Tumor necrosis factor-alpha (TNF-α) and IFN-γ] will be assessed at baseline, within 24-36 hours, then weekly for 4 weeks after TCZ administration;

    Measured: baseline, 24-36 hour, then weekly for 4 weeks after administration of TCZ

  2. Presence of HLH disease activity for each subject following TCZ administration

    HLH disease activity markers will be assessed for each subject (fever, ferritin, cardiopulmonary support requirements, cytopenias, coagulation tests, etc.)

    Measured: within 1 week of administration of TCZ

  3. Degree of hepatic function, cytopenias and infection in subjects following administration of TCZ

    Degree of hepatic function, presence (or absence) of cytopenia/infection will be assessed based on changes in laboratory and clinical markers following administration of TCZ.

    Measured: up to 1 year of administration of TCZ

  4. Overall survival of subjects

    Overall survival of subjects will include survival to day 100, and survival to completion of therapy (HSCT for primary HLH, and end of induction therapy for secondary HLH).

    Measured: day 100 and survival to completion of therapy (blood/marrow transplant, if applicable)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionMay 2021
  4. Study completionMay 2021

Why it stopped: No subjects were enrolled

Resources

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02007239
Sponsor's protocol ID
13-010459
Status last verified
Mar 2022
First submitted
5 Dec 2013
Last updated
28 Mar 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Henter JI, Samuelsson-Horne A, Arico M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G; Histocyte Society. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002 Oct 1;100(7):2367-73. doi: 10.1182/blood-2002-01-0172.

    PubMed 12239144

  • Tang Y, Xu X, Song H, Yang S, Shi S, Wei J, Pan B, Zhao F, Liao C, Luo C. Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome. Br J Haematol. 2008 Oct;143(1):84-91. doi: 10.1111/j.1365-2141.2008.07298.x. Epub 2008 Jul 31.

    PubMed 18673367

  • Navarro-Millan I, Singh JA, Curtis JR. Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting the interleukin-6 receptor. Clin Ther. 2012 Apr;34(4):788-802.e3. doi: 10.1016/j.clinthera.2012.02.014. Epub 2012 Mar 22.

    PubMed 22444783

  • Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, Nichols KE, Suppa EK, Kalos M, Berg RA, Fitzgerald JC, Aplenc R, Gore L, Grupp SA. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013 Jun 27;121(26):5154-7. doi: 10.1182/blood-2013-02-485623. Epub 2013 May 15.

    PubMed 23678006

  • Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. doi: 10.1056/NEJMoa1215134. Epub 2013 Mar 25.

    PubMed 23527958

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing tocilizumab in people with Hemophagocytic Lymphohistiocytosis, run by Children's Hospital of Philadelphia 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 8 inclusion and 14 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: withdrawn, as of the sponsor's last update on 28 Mar 2022. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Reduction in serum interferon-gamma levels after tocilizumab (TCZ) administration (time frame: baseline, 24 -36 hours, and 4-7 days after administration of TCZ). 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 NCT02007239, which also lists 5 linked publications.

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 28 Mar 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in