Alemtuzumab or Tocilizumab in Combination with Etoposide and Dexamethasone in Treating Patients with Hemophagocytic Lymphohistiocytosis
This phase II trial studies how well alemtuzumab or tocilizumab in combination with etoposide and dexamethasone work in treating patients with hemophagocytic lymphohistiocytosis. Hemophagocytic lymphohistiocytosis is a disorder that causes abnormal over activity of the immune system. Immunosuppressive therapy, using drugs such as alemtuzumab, tocilizumab, etoposide, and dexamethasone, may decrease the body’s immune system activity and prevent the immune system from causing damage to organs.
Inclusion Criteria
- Sign an Institutional Review Board (IRB)-approved informed consent document
- A documentation of diagnosis of hemophagocytic lymphocytosis, either newly diagnosed or relapsed/refractory by the treating physician and the principal investigator (PI) in the patients chart; it must be noted that no diagnostic criteria have been established for diagnosis of HLH in adult patients as this was a hitherto poorly identified and considered to be a very rare disease in adults; adult HLH seems to occur more frequently post malignancy and has a more fulminant course than pediatric HLH; in the absence of standard diagnostic guidelines if the patient's symptoms are highly suspicious for HLH and after an adequate work-up to rule out alternate potential alternate etiologies is performed we will treat the patient for HLH as missing the diagnosis is associated with high mortality; these patients will be discussed with the PI (Dr. Daver) prior to enrollment in all such cases
- Serum creatinine =< 3.0 mg/dL
- Total bilirubin =< 5.0 mg/dL
- If organ dysfunction is thought to be related to the HLH process this must be clearly documented in the chart and the patients may be enrolled on study irrespective of creatinine and bilirubin levels
- Women of childbearing potential must practice contraception; females of childbearing potential: recommendation is for 2 effective contraceptive methods during the study; adequate forms of contraception are double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, Depo Provera, or injectable contraceptives, intrauterine devices, and tubal ligation; male patients with female partners who are of childbearing potential: recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, prior to study entry and for at least 3 months after the last dose of study drug
- Negative urine pregnancy test and/or serum pregnancy test within 7 days of initiation of therapy
- Male patients with female partners who are of childbearing potential: recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, prior to study entry and for at least 3 months after the last dose of study drug
Exclusion Criteria
- Pregnant and breast feeding women
- Any serious/and or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures
- Patients unwilling or unable to comply with the protocol
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02385110.
PRIMARY OBJECTIVES:
I. To determine the overall response rate (ORR) of alemtuzumab or tocilizumab in combination with etoposide and dexamethasone in patients with hemophagocytic lymphohistiocytosis (HLH).
SECONDARY OBJECTIVES:
I. To determine the safety of alemtuzumab or tocilizumab in combination with etoposide and dexamethasone in patients with HLH.
II. To determine the median time to response, duration of response, disease-free survival (DFS), and overall survival (OS) of alemtuzumab or tocilizumab in combination with etoposide and dexamethasone in patients with HLH.
III. To determine the rates of partial and complete response at 8 weeks.
IV. To determine the incidence of serious infection and other adverse events by week 8 and prior to initiation of hematopoietic stem cell transplant (HSCT) preparative regimen (or week 24, if HSCT preparative regimen not yet begun).
V. To determine the overall survival to the initiation of HSCT preparative regimen (or week 24, if HSCT preparative regimen not begun).
VI. To determine the incidence and median time to reactivation prior to initiation of HSCT preparative regimen (or week 24, if HSCT preparative regimen not yet begun).
VII. To determine overall survival to day +100 after HSCT, for patients who have undergone HSCT within 6 months of study entry.
VIII. To determine the induction mortality (mortality within first 4 weeks and 8 weeks of initiation of therapy) for patients with HLH treated with this combination.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP 1: INDUCTION PHASE (WEEKS 1-8): Patients receive alemtuzumab intravenously (IV) over approximately 2 hours or subcutaneously (SC) on days 1-4, etoposide IV once weekly, and dexamethasone IV on days 1-7 and then orally (PO) daily. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE (WEEKS 9-24): Patients receive alemtuzumab IV once every 4 weeks and dexamethasone PO thrice weekly (Monday, Wednesday, and Friday). Treatment continues for up to 16 weeks in the absence of disease progression or unacceptable toxicity.
GROUP 2: INDUCTION PHASE (WEEKS 1-8): Patients receive tocilizumab IV over 60 minutes on day 1 or 2 and etoposide and dexamethasone as in Group 1. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE (WEEKS 9-24): Patients receive dexamethasone as in Group 1.
*NOTE: Deviations from the planned therapy for the induction phase and/or maintenance phase may be made at the discretion of the treating physician.
After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorNaval G. Daver
- Primary ID2014-0989
- Secondary IDsNCI-2015-00526, 00000363
- ClinicalTrials.gov IDNCT02385110