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

NCT00334672 | Unknown Phase 3

• 5 other identifiers: CDR0000481605CCLG-LCH-2006-02EU-20619UKCCSG-HLH-2004EUDRACT-2005-002187-28
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Nonneoplastic Condition

Keywords

hemophagocytic lymphohistiocytosis

Outcome Measures

Primary Outcomes (1)

• Survival

Interventions

anti-thymocyte globulin BIOLOGICAL

busulfan DRUG

cyclophosphamide DRUG

cyclosporine DRUG

dexamethasone DRUG

etoposide DRUG

methotrexate DRUG

mycophenolate mofetil DRUG

therapeutic hydrocortisone DRUG

laboratory biomarker analysis OTHER

allogeneic hematopoietic stem cell transplantation PROCEDURE

biopsy PROCEDURE

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Cancer and Leukaemia Group: lead

Study Sites (13)

Birmingham Children's Hospital

Birmingham, England, B4 6NH, United Kingdom

Location

Institute of Child Health at University of Bristol

Bristol, England, BS2 8AE, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

Watford General Hospital

Herts, England, WD18 0HB, United Kingdom

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, L12 2AP, United Kingdom

Location

Great Ormond Street Hospital for Children

London, England, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, England, M27 4HA, United Kingdom

Location

Children's Hospital - Sheffield

Sheffield, England, S10 2TH, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, AB25 2ZG, United Kingdom

Location

Royal Hospital for Sick Children

Edinburgh, Scotland, EH9 1LF, United Kingdom

Location

Royal Hospital for Sick Children

Glasgow, Scotland, G3 8SJ, United Kingdom

Location

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Interventions

Antilymphocyte Serum; Busulfan; Cyclophosphamide; Cyclosporine; Dexamethasone; Etoposide; Methotrexate; Mycophenolic Acid; Hydrocortisone; Biopsy

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Vasanta Nanduri, MD

  Watford General Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 7, 2006
• First Posted: June 8, 2006
• Study Start: March 1, 2006
• Primary Completion: November 1, 2010
• Last Updated: September 17, 2013

Record last verified: 2009-06

Locations

GB (13)