A Study to Evaluate Emapalumab in Adults with Hemophagocytic Lymphohistiocytosis


About this study

The primary purpose of this study is to assess the effectiveness of emapalumab in adult patients with Hemophagocytic Lymphohistiocytosis (HLH), as measured by Overall Response Rate.  

Secondary objectives are to assess the effectiveness of emapalumab as measured by overall survival, time to response, best response on treatment, duration of response; to evaluate the safety and tolerability of emapalumab; to determine the pharmacokinetic (PK) profile of emapalumab; and to determine the pharmacodynamic (PD) profile of emapalumab.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male and female patients, aged 18 and older at the time of HLH diagnosis.
  • Fulfilment of HLH-2004 clinical criteria; i.e., five of the eight criteria below:
    • Fever;
    • Splenomegaly;
    • Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin <90 g/L; platelets < 100 x 10^9/L; neutrophils <1 x 10^9/L);
    • Hypertriglyceridemia  (fasting  triglycerides  ≥ 3  mmol/L  or ≥ 265 mg/dL)  and/or  hypofibrinogenemia  (fibrinogen ≤1.5 g/L);
    • Hemophagocytosis in bone marrow, spleen or lymph nodes;
    • Low or absent natural killer (NK)cell activity;
    • Ferritin ≥ 500 µg/L;
    • Soluble CD25 (sCD25; i.e., soluble IL2 receptor) ≥ 2400 U/mL (or equivalent, in case the local lab uses different units).
  • Patients diagnosed with M-HLH must be treatment naïve; patients diagnosed with HLH driven by any other etiology or idiopathic can be either treatment naïve or treatment experienced.
  • Patients with non-malignancy-associated HLH who have already received conventional therapy for HLH must have failed prior treatment as per the treating physician`s judgement. At the time of enrolment, eligible treatment experienced patients may or may not be receiving conventional therapy.
  • JAK inhibitors, if administered, must be discontinued before emapalumab initiation.
  • Informed consent signed by the patient or by the patient’s legally authorized representative(s) (as required by local law).
  • Willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug, if female and of childbearing potential.

Exclusion Criteria:

  • Primary HLH (documented by the presence of known causative genetic mutations or by the presence of family history).
  • Current (within 60 days from SD0) or scheduled administration of therapies known to trigger the cytokine release syndrome (e.g., chimeric antigen receptor (CAR)-modified T cells, bispecific T cell- engaging antibodies).
  • Current (within 60 days from SD0) or scheduled administration of PD-1/PD-L1/CTLA-4 inhibitors.
  • Life-expectancy associated with the underlying disease (triggering HLH) < 3 months.
  • Ongoing participation in an investigational trial, or administration of any investigational treatment within 30 days from Screening.
  • History of hypersensitivity or allergy to any components of emapalumab.
  • Active mycobacteria, Histoplasma capsulatum, or Leishmania infections.
  • Evidence of latent tuberculosis.
  • Infection with HIV (HIV ELISA or PCR positive), hepatitis B (HBsAg positive), Hepatitis C (anti-HCV positive) unless the viral load by PCR is negative.
  • Concomitant diseases that in the opinion of the Investigator may significantly affect the likelihood of a response to treatment and/or the assessment of emapalumab safety and/or efficacy.
  • Receipt of a bacille Calmette-Guerin (BCG) vaccine within 12 weeks prior to Screening.
  • Receipt of a live or attenuated live (other than BCG) vaccine within 6 weeks prior to Screening.
  • Pregnancy or lactation (female patients).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Sameer Parikh, M.B.B.S.

Contact us for the latest status

Contact information:

Department of Medicine - Clinical Trials Unit

(507) 266-1944


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