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Combination Chemotherapy Followed By Donor Stem Cell Transplant in Treating Patients With Hemophagocytic Lymphohistiocytosis
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), April 2008
Sponsored by: Children's Cancer and Leukaemia Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00334672
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of hemophagocytic lymphohistiocytosis cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more hemophagocytic lymphohistiocytosis cells. A donor stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Cyclosporine and methotrexate may stop this from happening.

PURPOSE: This phase III trial is studying how well combination chemotherapy followed by a donor stem cell transplant works in treating patients with hemophagocytic lymphohistiocytosis.


Condition Intervention Phase
Precancerous/Nonmalignant Condition
Drug: anti-thymocyte globulin
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: dexamethasone
Drug: etoposide
Drug: methotrexate
Drug: mycophenolate mofetil
Drug: therapeutic hydrocortisone
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: biopsy
Procedure: laboratory biomarker analysis
Phase III

Drug Information available for: Cyclophosphamide Etoposide Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Hydrocortisone Cortisol 21-phosphate Cortisol succinate Hydrocortamate Hydrocortisone 21-sodium succinate Hydrocortisone acetate Hydrocortisone cypionate Hydrocortisone hemisuccinate Proctofoam-HC Methotrexate Cyclosporin Cyclosporine Etoposide phosphate Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Busulfan
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Hemophagocytic Lymphohistiocytosis

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Survival [ Designated as safety issue: No ]

Estimated Enrollment: 288
Study Start Date: March 2006
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Newly diagnosed hemophagocytic lymphohistiocytosis (HLH) meeting 1 of the following criteria*:

    • Diagnosis by molecular/genetic methods
    • Diagnosis by meeting 5 out of 8 of the following criteria:

      • Clinical criteria:

        • Fever
        • Splenomegaly
      • Laboratory criteria:

        • Cytopenias affecting ≥ 2 of 3 lineages in the peripheral blood, including the following:

          • Hemoglobin < 9.0 g/dL (< 10.0 g/dL in infants < 4 weeks of age)
          • Platelet count < 100,000/mm^3
          • Neutrophil count < 1,000/mm^3
        • Hypertriglyceridemia and/or hypofibrinogenemia:

          • Fasting triglycerides ≥ 3.0 mmol/L (i.e., ≥ 265 mg/dL)
          • Fibrinogen ≤ 1.5 g/L
      • Histopathologic criteria:

        • Hemophagocytosis in bone marrow, spleen, or lymph nodes

          • No evidence of malignancy
      • New diagnostic criteria:

        • Low or absent natural killer (NK) cell activity
        • Ferritin ≥ 500 mcg/L
        • Soluble CD25 (i.e., soluble interleukin-2 receptor) ≥ 2,400 U/mL NOTE: *Patients who do not meet the diagnostic criteria for HLH but who have a strong clinical suspicion of HLH may be eligible at the discretion of the investigator
  • Primary HLH (i.e., familial hemophagocytic lymphohistiocytosis [FLH]) OR secondary HLH (i.e., severe acquired form of HLH)
  • Acceptable donor meeting 1 of the following criteria:

    • HLA-identical related donor
    • Matched unrelated donor
    • Mismatched unrelated donor
    • Familial haploidentical donor

PATIENT CHARACTERISTICS:

  • Not specified

PRIOR CONCURRENT THERAPY:

  • No prior cytotoxic treatment for HLH
  • No prior cyclosporine treatment for HLH
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00334672

Locations
Ireland
Our Lady's Hospital for Sick Children Crumlin Recruiting
Dublin, Ireland, 12
Contact: Fin Breatnach, MD, FRCPE     353-1-409-6659     fin.breatnach@olhsc.ie    
United Kingdom, England
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Amos Burke, MD     44-1223-348-151        
Birmingham Children's Hospital Recruiting
Birmingham, England, United Kingdom, B4 6NH
Contact: Martin W. English, MD     44-121-333-8412     martin.english@bch.nhs.uk    
Children's Hospital - Sheffield Recruiting
Sheffield, England, United Kingdom, S10 2TH
Contact: Mary P. Gerrard, BSc, MBChB, FRCP, FRCPCH     44-114-271-7366     mary.gerrard@sch.nhs.uk    
Great Ormond Street Hospital for Children Recruiting
London, England, United Kingdom, WC1N 3JH
Contact: Gill Levitt, MD     44-20-7405-9200 ext. 0073        
Queen's Medical Centre Recruiting
Nottingham, England, United Kingdom, NG7 2UH
Contact: Martin Hewitt, MD, BSc, FRCP, FRCPCH     44-115-924-9924 ext. 63394     martin.hewitt@nuh.nhs.uk    
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Adam Glaser, MD     44-113-206-4984     adam.glaser@leedsth.nhs.uk    
Leicester Royal Infirmary Recruiting
Leicester, England, United Kingdom, LE1 5WW
Contact: Mabrouk Madi, MD     44-116-258-5959        
Middlesex Hospital Recruiting
London, England, United Kingdom, W1T 3AA
Contact: Ananth Shankar, MD     44-20-7380-9300 ext. 9950        
Oxford Radcliffe Hospital Recruiting
Oxford, England, United Kingdom, 0X3 9DU
Contact: Kate Wheeler, MD     44-186-522-1066        
Institute of Child Health at University of Bristol Recruiting
Bristol, England, United Kingdom, BS2 8AE
Contact: Pamela Kearns, MD     44-117-342-0205        
Royal Liverpool Children's Hospital, Alder Hey Recruiting
Liverpool, England, United Kingdom, L12 2AP
Contact: Heather P. McDowell, MD     44-151-293-3679        
Royal Manchester Children's Hospital Recruiting
Manchester, England, United Kingdom, M27 4HA
Contact: Bernadette Brennan, MD     44-161-922-2227     bernadette.brennan@cmmc.nhs.uk    
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Mary Taj, MD     44-20-8642-6011 ext. 3089        
Sir James Spence Institute of Child Health Recruiting
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Contact: Juliet Hale, MD     44-191-282-4101     j.p.hale@ncl.ac.uk    
Southampton General Hospital Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Janice A. Kohler, MD, FRCP     44-23-8079-6942        
Watford General Hospital Recruiting
Herts, England, United Kingdom, WD18 0HB
Contact: Vasanta Nanduri, MD     44-192-321-7992        
United Kingdom, Northern Ireland
Royal Belfast Hospital for Sick Children Recruiting
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Contact: Anthony McCarthy, MD     44-289-063-3631     anthonymcarthy@royalhospital.n.i.nhs.uk    
United Kingdom, Scotland
Royal Aberdeen Children's Hospital Recruiting
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Contact: Veronica Neefjes     44-1224-550-217        
Royal Hospital for Sick Children Recruiting
Glasgow, Scotland, United Kingdom, G3 8SJ
Contact: Milind D. Ronghe, MD     44-141-201-9309        
Royal Hospital for Sick Children Recruiting
Edinburgh, Scotland, United Kingdom, EH9 1LF
Contact: W. Hamish Wallace, MD     44-131-536-0426        
United Kingdom, Wales
Childrens Hospital for Wales Recruiting
Cardiff, Wales, United Kingdom, CF14 4XW
Contact: Heidi Traunecker, MD, PhD     44-29-2074-2285     heidi.traunecker@cardiffandvale.wales.nhs.uk    
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Investigators
Study Chair: Vasanta Nanduri, MD Watford General Hospital
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000481605, CCLG-LCH-2006-02, EU-20619, UKCCSG-HLH-2004, EUDRACT-2005-002187-28
Study First Received: June 7, 2006
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00334672  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
hemophagocytic lymphohistiocytosis

Study placed in the following topic categories:
Hemophagocytic lymphohistiocytosis
Dexamethasone
Hydrocortisone
Lymphohistiocytosis, Hemophagocytic
Cyclosporine
Precancerous Conditions
Cortisol succinate
Clotrimazole
Miconazole
Tioconazole
Cyclophosphamide
Cyclosporins
Etoposide phosphate
Folic Acid
Antilymphocyte Serum
Lymphatic Diseases
Histiocytosis
Busulfan
Mycophenolate mofetil
Methotrexate
Hydrocortisone acetate
Etoposide
Dexamethasone acetate

Additional relevant MeSH terms:
Antimetabolites
Anti-Inflammatory Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Reproductive Control Agents
Hormones
Therapeutic Uses
Antifungal Agents
Abortifacient Agents
Alkylating Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Reticuloendotheliosis
Antineoplastic Agents, Hormonal
Gastrointestinal Agents
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Glucocorticoids
Pharmacologic Actions
Neoplasms
Autonomic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on January 16, 2009