Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis
An Open Label Phase II Pilot Study of Hybrid ImmunoTherapy(ATG/Dexamethasone/Etoposide) for Hemophagocytic LymphoHistiocytosis:HIT-HLH
1 other identifier
interventional
31
2 countries
15
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Apr 2010
Longer than P75 for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2010
CompletedFirst Submitted
Initial submission to the registry
April 13, 2010
CompletedFirst Posted
Study publicly available on registry
April 15, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2016
CompletedResults Posted
Study results publicly available
October 19, 2020
CompletedOctober 19, 2020
September 1, 2020
5.6 years
April 13, 2010
August 28, 2020
September 21, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
8 Weeks
Secondary Outcomes (5)
Time to Response
8 Weeks
Overall Survival
up to day 180
Number of Participants Who Experienced Reactivation
up to 180 days
Overall Survival to Day +100
up to day 280
Disease Status at BMT
up to day 180
Study Arms (1)
Induction Therapy
EXPERIMENTALATG, 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
Interventions
ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
Phoenix Children's Hospital
Phoenix, Arizona, 85254, United States
University of California, San Francisco Department of Pediatrics
San Francisco, California, 94143, United States
Stanford University
Stanford, California, 94305, United States
University of Colorado
Aurora, Colorado, 80045, United States
Nemours
Wilmington, Delaware, 19803, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Nemours
Jacksonville, Florida, 32827, United States
Florida All Children's Hospital
St. Petersburg, Florida, 33701, United States
Tulane University Medical Center
New Orleans, Louisiana, 70118, United States
Children's Hospital Boston
Boston, Massachusetts, 02115, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Oregon Health and Science University
Portland, Oregon, 21703, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19145, United States
Texas Children's Cancer Center/Baylor College of Medicine
Houston, Texas, 77030, United States
The Hospital for Sick Children
Toronto, Ontario, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This is a single arm study.
Results Point of Contact
- Title
- Michael Jordan, MD
- Organization
- Cincinnati Children's Hospital Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Jordan, MD
Children's Hospital Medical Center, Cincinnati
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 13, 2010
First Posted
April 15, 2010
Study Start
April 1, 2010
Primary Completion
November 1, 2015
Study Completion
April 1, 2016
Last Updated
October 19, 2020
Results First Posted
October 19, 2020
Record last verified: 2020-09