Clinical Trials /

Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic Lymphohistiocytosis

NCT02385110

Description:

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.

Related Conditions:
  • Hemophagocytic Lymphohistiocytosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic Lymphohistiocytosis
  • Official Title: Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic Lymphohistiocytosis

Clinical Trial IDs

  • ORG STUDY ID: 2014-0989
  • SECONDARY ID: NCI-2015-00526
  • NCT ID: NCT02385110

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
AlemtuzumabCAMPATH-1H, CampathGroup 1: Alemtuzumab + Etoposide + Dexamethasone
EtoposideVePesidGroup 1: Alemtuzumab + Etoposide + Dexamethasone
DexamethasoneDecadronGroup 1: Alemtuzumab + Etoposide + Dexamethasone
MethotrexateGroup 1: Alemtuzumab + Etoposide + Dexamethasone
TocilizumabGroup 2: Etoposide + Dexamethasone + Tocilizumab

Purpose

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.

Detailed Description

      Study Treatment:

      If you are found to be eligible to take part in this study, your doctor will assign you to
      either Group 1 or Group 2.

      You will receive the study treatment in 2 parts. The first part of the study will last about
      8 weeks (Weeks 1-8) and will be called the "induction phase". The second part of the study
      will start after the induction phase and will last about 16 weeks (Weeks 9-16). This part
      will be called the "maintenance phase". However, the parts of the study may be longer or
      shorter depending on if/how the disease responds to the treatment, how the biomarkers react
      to treatment, and what the doctor thinks is in your best interest.

        -  If you are in Group 1, you will receive alemtuzumab by vein over 2 hours or through an
           injection under the skin every day on Days 1-4 of the induction phase and about 1 time
           every 4 weeks during the maintenance phase.

        -  If you are in Group 2, you will receive tocilizumab by vein over 60 minutes on Day 1 or
           Day 2 of the Induction phase. Tocilizumab will not be given in the Maintenance Phase.

      Participants in both Groups 1 and 2 will receive etoposide by vein about 1 time each week
      during the induction phase. You will not receive it in the maintenance phase unless the
      disease stops responding to the study drugs. At that point, you may begin to receive
      etoposide again. The study doctor will tell you more about this.

      The length of time it takes to infuse the study drugs will be different from patient to
      patient and will depend on rate of injection. Your doctor will discuss this with you.

      Participants in both Groups 1 and 2 will receive dexamethasone by vein on Days 1-7 of the
      induction phase. After this, you will take pills of dexamethasone every day during the
      induction phase. In the maintenance phase, you will take these pills 3 times each week with
      at least a day between each dose (for example, Monday, Wednesday, and Friday).

      Your dose of the study drugs may be raised, lowered, and/or delayed if the doctor thinks it
      is in your best interest.

      If the disease involves the central nervous system during the Induction phase, you may
      receive methotrexate. Methotrexate is given 1 time a week for 5 weeks.

      Study Visits:

      You will have physical exams on the following days:

        -  Day 1,

        -  Every week for the first 4 weeks,

        -  Every 2 weeks during the next 4 weeks,

        -  Every 4 weeks during the next 16 weeks, and

        -  Every 8 weeks after that.

      Blood (about 3 tablespoons) will be drawn for routine tests on the following days. During the
      first 4 weeks, these tests must be performed at MD Anderson. After that, these can be
      performed at a local clinic:

        -  Day 1,

        -  Two (2) times each week for the first 4 weeks,

        -  Every week for the next 4 weeks,

        -  Every 2 weeks for the next 16 weeks, and

        -  Every 4 weeks after that.

      You will have a bone marrow aspiration/biopsy 4 weeks after starting the study treatment and
      then every 4-12 weeks after that.

      At any time that the doctor thinks it is needed, you may have additional blood draws or bone
      marrow aspirations/biopsies to check the status of the disease. If you receive treatment for
      longer than 24 weeks, the timing of these procedures may be changed if the study doctor
      thinks it is in your best interest.

      Length of Study:

      You may continue taking the study drug for as long as the doctor thinks it is in your best
      interest. You will no longer be able to take the study drug if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      Your participation on the study will be over after the follow-up visits.

      End-of-Study Visit:

      If you are taken off or if you leave the study before you have received treatment for 24
      weeks, the following tests and procedures will be performed within 30 days (+/- 7 days) of
      the last dose of the study drug:

        -  Blood (about 2-3 tablespoons) will be drawn for routine tests.

        -  If the doctor thinks it is needed, you will have a bone marrow aspirate to check the
           status of the disease.

      If you cannot make it to MD Anderson for this visit, these procedures may be done with a
      local doctor and the records can be forwarded to the study doctor.

      Follow-Up:

      If you respond to the study drugs, you will be followed every 3-6 months for up to 5 years
      after completion of treatment. You will be called and asked about how you are doing. Each
      call will last about 5-10 minutes.
    

Trial Arms

NameTypeDescriptionInterventions
Group 1: Alemtuzumab + Etoposide + DexamethasoneExperimentalInduction Phase: Participants receive Alemtuzumab daily on Days 1 - 4 with weekly Etoposide, and Dexamethasone by vein on Days 1-7 during the 8-week induction phase. Participants with central nervous system involvement receive intrathecal methotrexate 12 mg once a week for 5 weeks during the Induction Phase. Dexamethasone by vein on Days 1-7 of the induction phase. Maintenance Phase: The maintenance phase will last 16 weeks and starts after the Induction Phase. Participants receive Alemtuzumab once every 4 weeks and Dexamethasone three times per week during the maintenance phase. Participants who have evidence of budding relapse during the maintenance phase may revert back to receiving Etoposide. 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.
  • Alemtuzumab
  • Etoposide
  • Dexamethasone
  • Methotrexate
Group 2: Etoposide + Dexamethasone + TocilizumabExperimentalInduction Phase: Participants receive Tocilizumab by vein over 60 minutes on Day 1 or Day 2 of the Induction phase. Participants receive Alemtuzumab daily on Days 1 - 4 with weekly Etoposide and Dexamethasone by vein on Days 1-7 during the 8-week induction phase. Participants with central nervous system involvement receive intrathecal methotrexate 12 mg once a week for 5 weeks during the Induction Phase. Maintenance Phase: The maintenance phase will last 16 weeks and starts after the Induction Phase. Tocilizumab not given in the Maintenance Phase. Dexamethasone three times per week during the maintenance 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
  • Alemtuzumab
  • Etoposide
  • Dexamethasone
  • Methotrexate
  • Tocilizumab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) of Alemtuzumab or Tocilizumab in Combination With Etoposide and Dexamethasone for the Treatment of Adult Patients With Hemophagocytic Lymphohistiocytosis
Time Frame:8 weeks
Safety Issue:
Description:Overall response rate (ORR), defined as complete response (CR) and/or partial response (PR) and/or parameter improvements (PI).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Leukemia
  • Hemophagocytic lymphohistiocytosis
  • HLH
  • Alemtuzumab
  • CAMPATH-1H
  • Campath
  • Etoposide
  • VePesid
  • Dexamethasone
  • Decadron
  • Methotrexate
  • Phone call

Last Updated

May 20, 2019