Pilot Study of Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients With Life Threatening Hemophagocytic Disorders

June 23, 2005 updated by: Fairview University Medical Center

OBJECTIVES: I. Determine the efficacy of unrelated donor hematopoietic stem cell transplantation in the treatment of patients with life threatening hemophagocytic disorders.

II. Determine the rate of disease free survival, incidence of graft failure, and incidence of graft versus host disease in these patients after undergoing this treatment regimen.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

PROTOCOL OUTLINE: Patients receive oral busulfan twice a day on days -9 to -6; cyclophosphamide IV over 1 hour on days -5 to -2; etoposide IV over 4 hours on days -5 to -3; and anti-thymocyte globulin IV twice a day on days -2 and -1 and days 1 and 2. Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. Filgrastim (G-CSF) is administered subcutaneously beginning on day 1 and continuing until blood counts recover. Patients receive graft versus host disease prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1-4 hours (orally once the patients resumes eating) every 12 hours (every 8 hours for pediatric patients) starting on or prior to day -3 and continuing up to 1 year.

Patients are followed at days 28 and 100, at 6 months and 1 year, and then annually for 5 years.

Study Type

Interventional

Enrollment

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Fairview University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 55 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Patients diagnosed with any of the following active but stable, or nonactive/quiescent, hemophagocytic disorders:

  • Hemophagocytic lymphohistiocytosis (HLH)
  • Fever greater than 38.5 degrees Celsius
  • Splenomegaly (greater than 3 cm below costal margin)
  • Hemophagocytosis in bone marrow or spleen or lymph nodes
  • Disease may be confirmed by positive family history
  • No evidence of malignancy
  • Hypertriglyceridemia and/or hypofibrinogenemia
  • Fasting triglycerides at least 2.0 mmol/L or at least 3 standard deviations above normal for age
  • Fibrinogen no greater than 1.5 g/L or no greater than 3 standard deviations above normal
  • Cytopenia (affecting at least 2 of 3 lineages in the peripheral blood)
  • Hemoglobin less than 9.0 g/L
  • Platelet count less than 100,000/mm3

X-linked lymphoproliferative disorder (XLP)

Two or more maternally related males manifesting at least one of the following XLP phenotypes:

  • Fulminant infectious mononucleosis
  • Dysgammaglobulinemia
  • Malignant lymphoma/lymphoproliferative disorder
  • Aplastic anemia
  • Lymphoid granulomatosis/vasculitis OR
  • A maternally related male in an established XLP kindred who has strong genetic (RFLP) linkage to the XLP locus

Chediak-Higashi syndrome

Partial oculocutaneous albinism (hair, skin, eyes)

Frequent bacterial infections

Large peroxidase positive granules in leukocytes of peripheral blood or bone marrow

Positive family history or parental consanguinity is supportive of the diagnosis

May not have entered accelerated phase as defined by any of the following:

  • Lymphadenopathy
  • Pancytopenia
  • Histiocytes with hemophagocytosis in bone marrow, lymph nodes, liver, or spleen

Viral associated hemophagocytic syndrome (VAHS)

Relapsed after prior therapy or supportive care

Diagnostic criteria as for HLH

No hemophagocytic disorders secondary to underlying malignancy

Patients 35 years of age and under must have a hematopoietic stem cell donor that is one of the following:

  • HLA A and B identical OR
  • Single HLA A or B serologic mismatch with DRB1 identity OR
  • HLA A or B serologic identity with a single DRB1 mismatch

Patients 36 to 55 years of age must have a hematopoietic stem cell donor that is one of the following:

  • HLA A and B and HLA DRB1 identical OR
  • Single HLA A or B serologic mismatch with DRB1 identity

Patients receiving umbilical cord blood must have an unrelated donor with no more than two antigen HLA A, B, or DRB1 mismatches

--Patient Characteristics--

Performance status: Karnofsky 70-100% OR Age less than 16 years: Lansky 50-100%

Life expectancy: Not severly limited by another disease

Hepatic: SGOT less than 3 times normal Bilirubin less than 2.5 mg/dL

Renal: Creatinine normal OR Creatinine clearance or glomerular filtration rate greater than 50% normal

Cardiovascular: If symptomatic, ventricular ejection fraction must be greater than 40% and must improve with exercise OR Shortening fraction normal on echocardiogram

Pulmonary:

  • If symptomatic, DLCO greater than 45% predicted (corrected for hemoglobin)
  • In children unable to perform pulmonary function testing, oxygen saturation must be greater than 95%

Other: HIV negative No significant active infections

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fairview University Medical Center

Investigators

  • Study Chair: K. Scott Baker, Fairview University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2000

Study Registration Dates

First Submitted

July 5, 2000

First Submitted That Met QC Criteria

July 5, 2000

First Posted (Estimate)

July 6, 2000

Study Record Updates

Last Update Posted (Estimate)

June 24, 2005

Last Update Submitted That Met QC Criteria

June 23, 2005

Last Verified

October 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 199/15106
  • UMN-MT-1997-08
  • UMN-MT-9708

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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