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Hemophagocytic LymphohistiocytosisPhase 2NCT01104025

Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis

A Phase 2 study testing ATG, rabbit, Etoposide and Methotrexate in people with Hemophagocytic Lymphohistiocytosis, run by Children's Hospital Medical Center, Cincinnati at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Despite good progress during the last decade, hemophagocytic lymphohistiocytosis (HLH) remains difficult to treat. Two different treatment regimens have been used successfully. The first one, a treatment regimen based on two drugs called etoposide and dexamethasone, has been used worldwide. Read more about this study

Who is it for?
Ages Up to 18 years
Conditions the study is for
Hemophagocytic Lymphohistiocytosis
What is being tested?
ATG, rabbit, Etoposide and Methotrexate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
15 sitesin 2 countries
Study dates
Apr 2010to Apr 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • diagnosis of hemophagocytic lymphohistiocytosis
  • Patients <18 years of age
  • The patient must have active disease at the time of enrollment
  • Patient's legal guardians must sign an Institutional Review Board approved consent form indicating their awareness of the investigational nature and the risks of this study.
  • Eligible subjects must be enrolled with the protocol coordinating center

Who cannot join

  • Recent treatment, within 3 months, with another therapeutic regimen for HLH
  • Known active malignancy
  • Known rheumatologic diagnosis which may be the underlying cause of HLH
  • Pregnancy (as determined by serum or urine test) or active breast feeding
  • Failure to provide signed informed consent

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites

  • University of Colorado

    Aurora, Colorado, 80045

  • Children's Hospital Boston

    Boston, Massachusetts, 02115

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Texas Children's Cancer Center/Baylor College of Medicine

    Houston, Texas, 77030

  • Nemours

    Jacksonville, Florida, 32827

  • Tulane University Medical Center

    New Orleans, Louisiana, 70118

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19145

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85254

  • Oregon Health and Science University

    Portland, Oregon, 21703

  • University of California, San Francisco Department of Pediatrics

    San Francisco, California, 94143

  • Florida All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stanford University

    Stanford, California, 94305

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Nemours

    Wilmington, Delaware, 19803

Other trials in United States

Canada1 site

  • The Hospital for Sick Children

    Toronto, Ontario

Other trials in Canada

About this study

Official title: An Open Label Phase II Pilot Study of Hybrid ImmunoTherapy(ATG/Dexamethasone/Etoposide) for Hemophagocytic LymphoHistiocytosis:HIT-HLH

Despite good progress during the last decade, hemophagocytic lymphohistiocytosis (HLH) remains difficult to treat. Two different treatment regimens have been used successfully. The first one, a treatment regimen based on two drugs called etoposide and dexamethasone, has been used worldwide. The second regimen, based on two drugs called Anti-thymocyte globulin (ATG) and prednisone, has been used mostly at one hospital in Paris, for over 15 years. With either regimen, about three quarters of treated children survive the most difficult time, the first two months after diagnosis. These two different regimens appear to work somewhat differently, and we suspect that combining them may give better results than either regimen alone. We are conducting this clinical trial to test the combination of ATG, dexamethasone, and etoposide for the treatment of HLH.

The purpose of this research study is to find out what effects (good and bad) this drug combination has on you and your HLH.

Read the detailed description

Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder first recognized almost 70 years ago.(1) Genetic and animal studies have indicated that the familial form of HLH is clearly due to a deficiency of cytotoxic killing. Patients with HLH present with a potentially fatal syndrome of 'hyperimmunity.' These patients have severe inflammation, associated with cytopenias and variably severe bone marrow, liver, or CNS damage. Tissue damage and mortality appear to be due to hypercytokinemia related to persistent immune hyperactivation. An animal model of HLH and correlative human studies all suggest that excessive and abnormal activation of T cells drives the pathophysiology of this disorder, and that suppressing this excessive activation is critical for successful therapy of HLH. It is believed a combination of the two proven induction regimens for hemophagocytic lymphohistiocytosis (HLH) (anti-thymocyte globulin (ATG)- and etoposide-based) will result in response rates and overall survival rates at eight weeks which are comparable or better than the current standard of care (induction therapy per the HLH-94 protocol).

Keywords
hemophagocytic lymphohistiocytosis, hybrid immunotherapy, dexamethasone, Etoposide, ATG,rabbit
Medical subject headings
Lymphohistiocytosis, Hemophagocytic

What participants receive

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

  • ATG, rabbitDrug

    Also called Thymoglobulin

    ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).

  • EtoposideDrug

    Also called Etopophos, Toposar, VePesid

    Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.

  • MethotrexateDrug

    Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients (CNS+ patients are those patients which have any of the following: elevated CSF (cerebral spinal fluid) protein or white count, seizures, focal or global neurologic deficit, MRI abnormalities consistent with CNS involvement by HLH.) in the following doses: age< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, >3 yrs: 12/15 mg. It will be administered (+/- 3 days) on day 7, 14, 21 and 42.

  • hydrocortisoneDrug

    Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients (CNS+ patients are those patients which have any of the following: elevated CSF (cerebral spinal fluid) protein or white count, seizures, focal or global neurologic deficit, MRI abnormalities consistent with CNS involvement by HLH.) in the following doses: age< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, >3 yrs: 12/15 mg. It will be administered (+/- 3 days) on day 7, 14, 21 and 42.

  • DexamethasoneDrug

    will be started with the ATG. It will be divided BID, given IV for at least 1 week before switching to PO. Dosing: 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days.

Study groups in NCT01104025
Study groupRoleWhat they receive
Induction TherapyExperimentalATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, >3 yrs: 12/15 mg, on day 7, 14, 21 and 42
Receives: Drug: ATG, rabbit; Drug: Etoposide; Drug: Methotrexate; Drug: hydrocortisone; Drug: Dexamethasone

What is being measured

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

  1. Overall Survival

    To determine the overall survival of patients with hemophagocytic lymphohistiocytosis at 8 weeks after an ATG/etoposide-based induction regimen and to determine the feasibility of this approach in the context of a multicenter clinical trial.

    Measured: 8 Weeks

Secondary outcomes (5)

  1. Time to Response

    To determine the median time to complete response during 8 weeks of therapy

    Measured: 8 Weeks

  2. Overall Survival

    To determine overall survival prior to the initiation of BMT (bone marrow transplant) preparative regimen (or day 180, if BMT preparative regimen not yet begun)

    Measured: up to day 180

  3. Number of Participants Who Experienced Reactivation

    To determine the frequency of disease reactivation prior to initiation of BMT preparative regimen (or day 180, if BMT preparative regimen not yet begun)

    Measured: up to 180 days

  4. Overall Survival to Day +100

    To determine overall survival to day +100 after BMT, for patients who have undergone BMT within 6 months of study entry

    Measured: up to day 280

  5. Disease Status at BMT

    To determine the rate of complete response at the time of BMT preparative regimen initiation

    Measured: up to day 180

Timeline

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

  1. First posted15 Apr 2010 (estimated)
  2. Study startApr 2010
  3. Primary completionNov 2015
  4. Study completionApr 2016

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
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01104025
Sponsor's protocol ID
HIT-HLH
Status last verified
Sep 2020
First submitted
13 Apr 2010
Last updated
19 Oct 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ATG, rabbit, Etoposide and Methotrexate in people with Hemophagocytic Lymphohistiocytosis, run by Children's Hospital Medical Center, Cincinnati at 15 sites in 2 countries.

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 5 inclusion and 5 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: finished, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Canada. 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?

Yes. Results are posted in the registry (first posted 19 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Survival (time frame: 8 Weeks). 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 NCT01104025.

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 19 Oct 2020.

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