International Registry for Severe Chronic Neutropenia

NCT ID: NCT00004342

Last Updated: 2020-10-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

1994-06-30

Brief Summary

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OBJECTIVES: I. Document the clinical course of severe chronic neutropenia (SCN).

II. Monitor and assess long term safety of primary treatment in SCN patients in the United States, Canada, Europe, and Australia.

III. Study the incidence and outcome of adverse events such as osteoporosis, splenomegaly, cytogenetic abnormalities, myelodysplastic syndrome, and leukemia.

IV. Evaluate growth and development and hematologic parameters. V. Monitor for clinically significant changes in primary treatment response over time.

VI. Establish a physician network to increase the understanding of SCN. VII. Establish a demographic database to allow for future research.

Detailed Description

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PROTOCOL OUTLINE:

Patients are treated by the referring physician as medically indicated. Clinical data are collected at baseline and then every 6 months.

Conditions

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Neutropenia

Study Design

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Observational Model Type

OTHER

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Adult Neutropenic Subject

Adult subjects with diagnosis of severe chronic neutropenia

No interventions assigned to this group

Minor Neutropenic Subject

Children under 18 years of age who are diagnosed with severe chronic neutropenia

No interventions assigned to this group

Parent of Minor Neutropenic Subjects

Parent of minor subjects (i.e., children under 18 years of age) who are diagnosed with severe chronic neutropenia

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. A confirmed diagnosis of severe chronic neutropenia based on documented absolute neutrophil counts of less than 0.5x109/L on at least three occasions in the three months prior to enrollment.
2. For subjects with presumed cyclic neutropenia, documentation of at least two neutrophil cycles is preferred. Documentation should include the nadirs with neutrophil counts of less than 200 followed by a clear increase in the counts generally to at least 500 to 1000 followed by a second nadir, usually expected to occur at about three weeks after the first nadir, i.e., cycling with a three week periodicity. Documentation with at least six weeks of counts and two expected nadirs is preferred.

Cases not showing clear oscillations will be categorized as congenital (if neutropenia or neutropenic complications appear to have occurred from birth) or idiopathic (if all symptoms in evidence point to an acquired disorder occurring after the first year of life).
3. Bone marrow aspiration consistent with the diagnosis of congenital, cyclic or idiopathic neutropenia. In all of these conditions, it is expected that the marrow aspirate evaluation at the time of neutropenia will show a deficiency of mature neutrophils. An exception is myelokathexis, a condition with large accumulations of neutrophils with pycnotic nuclei in the marrow. Bone marrow aspirates may show some dyspoiesis of the neutrophil lineage, but abnormalities of erythropoiesis or platelet formation are, in general, inconsistent with the diagnosis of SCN.
4. Normal cytogenetic evaluation. The only exception being cases of well documented severe congenital neutropenia with preferably previously documented normal cytogenetic evaluation will now be enrolled in the Registry at the time of evolution to leukemia.
5. History of recurrent infections (i.e., severe mouth ulcers, gingivitis and sinusitis).
6. Age greater than three months.
7. Independent of hematological parameters, subjects with the following diagnoses may be included: Shwachman-Diamond syndrome (SDS), glycogen storage disease type 1b (GSD1b), Barth syndrome, and Cohen's syndrome.
8. Subjects with moderately severe chronic neutropenia (i.e., ANC less than 1.0x109/L) and recurrent severe infections (i.e., deep tissue infections of subcutaneous areas, lungs, liver, etc.).
9. Immune neutropenia with positive anti-neutrophil antibodies meeting criteria in 1, 3, 5 and 6.
10. All SCN subjects originally enrolled in Amgen-sponsored SCN studies.

Exclusion Criteria

1. Neutropenia known to be drug induced
2. Primary myelodysplasia
3. Primary leukemia
4. Aplastic anemia
5. Known HIV disease
6. Systemic autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus
7. Chemotherapy-induced neutropenia (within the last 5 years)
Minimum Eligible Age

3 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Washington

OTHER

Sponsor Role collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role lead

Responsible Party

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David Chandler Dale

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David Chandler Dale

Role: STUDY_CHAIR

University of Washington

Locations

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Dana-Farber/Boston Children¹s Cancer and Blood Disorders Center

Boston, Massachusetts, United States

Site Status RECRUITING

University of Massachusetts

Worcester, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

St. Joseph's Children's Hospital

Paterson, New Jersey, United States

Site Status RECRUITING

University of Washington School of Medicine

Seattle, Washington, United States

Site Status RECRUITING

Monash University

Melbourne, Victoria, Australia

Site Status RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status RECRUITING

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status RECRUITING

Leeds Teaching Hospitals, Yorkshire Regional Centre for Paediatric Oncology & Haematology

Leeds, England, United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada Germany United Kingdom

Facility Contacts

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Akiko Shimamura, MD, PhD

Role: primary

617-919-6109

Peter Newburger, MD

Role: primary

508-856-4225

Kelly J. Walkovich, MD

Role: primary

734-647-2893

MaryAnn Bonilla

Role: primary

973-754-3230

Caterna Lovaglio, RN/CRA

Role: backup

973-754-3778

David Chandler Dale

Role: primary

206-543-7215

Graham Leischke, PhD

Role: primary

+61 3 9902 9720

Bonnie Paula Cham

Role: primary

204-787-4147

Yigal Dror, MD

Role: primary

+416-813-5630

Philippa McCaffrey

Role: backup

+416-813-8886

Connie Zeidler, Dr.med

Role: primary

+49-511-532-6710

Sonja Klein

Role: backup

Sally Kinsey, MD

Role: primary

+44-113-392-8191

References

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Dale DC, Bonilla MA, Boxer L, et al.: Development of AML/MDS in a subset of patients (PTS) with severe chronic neutropenia (SCN). Blood 84(10 suppl 1): 518a, 1994.

Reference Type BACKGROUND

Guerra J, Withers DA, Boxer LM. Myb binding sites mediate negative regulation of c-myb expression in T-cell lines. Blood. 1995 Sep 1;86(5):1873-80.

Reference Type BACKGROUND
PMID: 7655015 (View on PubMed)

Welte K, Dale D. Pathophysiology and treatment of severe chronic neutropenia. Ann Hematol. 1996 Apr;72(4):158-65. doi: 10.1007/s002770050156.

Reference Type BACKGROUND
PMID: 8624368 (View on PubMed)

Kalra R, Dale D, Freedman M, Bonilla MA, Weinblatt M, Ganser A, Bowman P, Abish S, Priest J, Oseas RS, Olson K, Paderanga D, Shannon K. Monosomy 7 and activating RAS mutations accompany malignant transformation in patients with congenital neutropenia. Blood. 1995 Dec 15;86(12):4579-86.

Reference Type BACKGROUND
PMID: 8541548 (View on PubMed)

Other Identifiers

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UW-730

Identifier Type: -

Identifier Source: secondary_id

199/11901

Identifier Type: -

Identifier Source: org_study_id

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