Clinical trial NCT00004342: International Registry for Severe Chronic Neutropenia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Neutropenia
Keywords: chronic neutropenia
disease-related problem/condition
hematologic disorders
neutropenia
rare disease
severe chronic neutropenia
Lead sponsor: National Center for Research Resources (NCRR)
Sponsor class: NIH
Collaborators: name: University of Washington
First posted: 1999-10-19
Enrollment: 1000
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients diagnosed with severe chronic neutropenia

Brief summary: 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: PROTOCOL OUTLINE:

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

Eligibility criteria: Inclusion Criteria - Subjects are eligible for enrollment if they meet the following 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)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber/Boston Children¹s Cancer and Blood Disorders Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Paterson
country: United States
facility: St. Joseph's Children's Hospital
state: New Jersey
city: Seattle
country: United States
facility: University of Washington School of Medicine
state: Washington
city: Melbourne
country: Australia
facility: Monash University
state: Victoria
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals, Yorkshire Regional Centre for Paediatric Oncology & Haematology
state: England
Study officials:
affiliation: University of Washington
name: David Chandler Dale
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: Welte K, Dale D. Pathophysiology and treatment of severe chronic neutropenia. Ann Hematol. 1996 Apr;72(4):158-65. doi: 10.1007/s002770050156.
citation: 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.