Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic Lymphohistiocytosis
Condition: Leukemia
MeSH terms: Lymphohistiocytosis, Hemophagocytic
Intervention: Alemtuzumab; Etoposide; Dexamethasone; Methotrexate; Phone Call; Tocilizumab
Intervention description: Group 1 and 2 Induction Phase: Alemtuzumab total dose of 1.0 mg/kg subcutaneously or by vein over 4 days (days 1-4) during the 8 week induction phase. Day 1 0.1 mg/kg, Day 2 0.3 mg/kg, Day 3 0.3 mg/kg, Day 4 0.3 mg/kg.
Group 1 Maintenance Phase: 0.2 mg/kg once every 4 weeks for 6 weeks.; Induction Phase: 150 mg/m2 given by vein once a week for 8 weeks.
Maintenance Phase: Participants who have evidence of refractory disease or budding relapse during the maintenance phase may revert back to receiving Etoposide.; Induction Phase: 10 mg/m2 for 1 week followed by Dexamethasone 5 mg/m2 for 2 weeks followed by Dexamethasone 2.5 mg/m2 for 2 weeks followed by Dexamethasone 1.25 mg/m2 for 2 weeks.
Maintenance Phase: 1.25 mg/m2 by mouth three times a week for 16 weeks.; Participants with central nervous system involvement receive intrathecal methotrexate 12 mg once a week for 5 weeks during the Induction Phase.; If participant responds to study drugs, they will receive a phone call by study staff every 3 - 6 months for up to 5 years after completion of treatment. Each call will last about 5-10 minutes.; Induction Phase: Tocilizumab at 4 to 8 mg/kg by vein. Day 1 0.1 mg/kg,Day 2 0.3 mg/kg, Day 3 0.3 mg/kg, Day 4 0.3 mg/kg.
Intervention MeSH terms: Dexamethasone; Methotrexate; Etoposide; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Hemophagocytic lymphohistiocytosis; HLH; Alemtuzumab; CAMPATH-1H; Campath; Etoposide; VePesid; Dexamethasone; Decadron; Methotrexate; Phone call

Summary:

      The goal of this clinical research study is to compare the effect of adding either
      alemtuzumab or tocilizumab to the drug combination of etoposide and dexamethasone in
      controlling HLH. The safety of the drug combinations will also be studied.

      This is an investigational study. Alemtuzumab, etoposide, tocilizumab, and dexamethasone are
      not FDA approved for the treatment of HLH. Etoposide is FDA approved and commercially
      available for the treatment of testicular cancer and lung cancer. Alemtuzumab is FDA approved
      and commercially available for the treatment of chronic lymphocytic leukemia. Dexamethasone
      is a steroid used to reduce inflammation. Tocilizumab is FDA approved and commercially
      available for the treatment of arthritis. The combination of alemtuzumab, etoposide,
      tocilizumab, and dexamethasone to treat HLH is investigational. The study doctor can explain
      how the drugs are designed to work.

      Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Sign an IRB-approved informed consent document.

          2. Patients must be >/= 18 years of age.

          3. • A documentation of diagnosis of hemophagocytic lymphocytosis, either newly diagnosed
             or relapsed/refractory by the treating physician and the 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. We have seen an increasing number of cases of HLH at our
             institution over the last 2 years partly due to referrals and partly due to better
             understanding of the disease through discussions with our collaborators Dr Kenneth
             McClain and Dr Carl Allen at TCH (experts in pediatric HLH). Adult HLH seems to occur
             more frequently post malignancy and has a more fulminant course than pediatric HLH.

          4. Continued from No. 3: The diagnostic criteria that have been traditionally used for
             children (HLH 1991 and HLH 2004) may not adequately diagnose HLH in adults. This is
             the first adult HLH protocol in the country. 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.

          5. Organ function as defined below (unless due to the HLH process): 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.

          6. 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.

          7. Negative urine pregnancy test and/or serum pregnancy test within 7 days of initiation
             of therapy.

          8. 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:

          1. Pregnant and breast feeding women

          2. 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

          3. Patients unwilling or unable to comply with the protocol.