Combination Chemotherapy Followed By Donor Stem Cell Transplant in Treating Patients With Hemophagocytic Lymphohistiocytosis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00334672
First received: June 7, 2006
Last updated: September 16, 2013
Last verified: June 2009
  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
Nonneoplastic Condition
Biological: anti-thymocyte globulin
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: dexamethasone
Drug: etoposide
Drug: methotrexate
Drug: mycophenolate mofetil
Drug: therapeutic hydrocortisone
Other: laboratory biomarker analysis
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: biopsy
Phase 3

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Hemophagocytic Lymphohistiocytosis

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334672

Locations
United Kingdom
Birmingham Children's Hospital
Birmingham, England, United Kingdom, B4 6NH
Institute of Child Health at University of Bristol
Bristol, England, United Kingdom, BS2 8AE
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Watford General Hospital
Herts, England, United Kingdom, WD18 0HB
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP
Great Ormond Street Hospital for Children
London, England, United Kingdom, WC1N 3JH
Royal Manchester Children's Hospital
Manchester, England, United Kingdom, M27 4HA
Children's Hospital - Sheffield
Sheffield, England, United Kingdom, S10 2TH
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom, G3 8SJ
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Investigators
Study Chair: Vasanta Nanduri, MD Watford General Hospital
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00334672     History of Changes
Other 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: September 16, 2013
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Lymphohistiocytosis, Hemophagocytic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Cyclosporins
Cyclosporine
Methotrexate
Mycophenolate mofetil
Dexamethasone
Etoposide
Mycophenolic Acid
BB 1101
Hydrocortisone-17-butyrate
Dexamethasone acetate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Dexamethasone 21-phosphate
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 31, 2014