ClinicalTrials.gov
ClinicalTrials.gov Menu

Patients Treated for Wiskott-Aldrich Syndrome (WAS) Since 1990

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02064933
Recruitment Status : Active, not recruiting
First Posted : February 17, 2014
Last Update Posted : November 21, 2018
Sponsor:
Collaborators:
Primary Immune Deficiency Treatment Consortium (PIDTC)
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

Wiskott - Aldrich syndrome (WAS) is a rare serious medical condition that causes problems both with the immune system and with easy bruising and bleeding. The immune abnormalities cause patients with WAS to be very susceptible to infections. Depending on the specific type of primary immune deficiency diseases, there are effective treatments, including antibiotics, cellular therapy and gene therapy, but studies of large numbers of patients are needed to determine the full range of causes, natural history, or the best methods of treatment for long term success.

This multicenter study combines retrospective, prospective and cross-sectional analyses of the transplant experiences for patients with WAS who have already received HCT since 1990, or who will undergo Hematopoietic cell transplant (HCT) during the study period. The retrospective and prospective portions of the study will address the impact of a number of pre and post-transplant factors on post-transplant disease correction and ultimate benefit from HCT and the cross-sectional portion of the study will assess the benefit of HCT 2 years post-HCT in consenting surviving patients.


Condition or disease
Wiskott-Aldrich Syndrome

Study Type : Observational
Estimated Enrollment : 541 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Analysis of Patients Treated for Wiskott-Aldrich Syndrome Since January 1, 1990 (RDCRN PIDTC-6904)
Study Start Date : June 2014
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Group/Cohort
Retrospective Cohort (Longitudinal Analysis)
Participants with WAS treated at consortium centers since 1990 who have received transplant (Stratum A) or gene therapy (Stratum B)
Prospective Cohort (Longitudinal Analysis)
Participants treated at consortium centers since 1990 who will receive transplant (Stratum A) or gene therapy (Stratum B)
Cross-Sectional Cohort (Cross-sectional Analysis)
Living participants with WAS who have received transplant (Stratum A) or gene therapy (Stratum B) at Consortium Centers 1990-Present And >= 2 Years Post-Transplant



Primary Outcome Measures :
  1. Longitudinal Analysis: Overall Survival From Time of HCT/Gene Therapy [ Time Frame: an expected average of 5 years ]
    The event analyzed is death from any cause. The time to this event is the time from HCT/gene therapy to death or last follow-up.

  2. Cross-Sectional Analysis: Proportion of Participants Achieving Full T Cell Reconstitution [ Time Frame: an expected average of 5 years ]

    Full T cell reconstitution is defined by all of the following:

    • CD3 cell count within normal range for age.
    • CD4 cell count within normal range for age.
    • CD8 cell count within normal range for age
    • Donor T cell chimerism > 95%
    • Lymphocyte proliferation to PHA. Proliferative responses to PHA within the normal range (at or above the lower limit of normal).

    When possible the proliferation to PHA should be calculated as a percentage of the lower limit of normal controls for that laboratory; alternatively, the lower limit of normal controls for the day may be used


  3. Cross-Sectional Analysis: Proportion of Participants Achieving Full B Cell Reconstitution [ Time Frame: an expected average of 5 years ]

    Full B cell reconstitution is defined by all of the following:

    • Quantitative immunoglobulins (IgG, IgM, and IgA) within normal range; each immunoglobulin level will be assessed separately.
    • Serologic confirmation of post immunization tetanus titer in protective range.
    • Serologic confirmation of post immunization pneumococcal titers in protective range (protective titers for > 50% of the serotypes contained in the vaccine) following immunization

  4. Cross-Sectional Analysis: Proportion of Participants Achieving Resolution of thrombocytopenia [ Time Frame: an expected average of 5 years ]
    Resolution of thrombocytopenia defined by Platelets ≥ 150,000/microliter (transfusion independent for at least 7 consecutive days)

  5. Cross-Sectional Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL [ Time Frame: an expected average of 5 years ]
    Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL is defined as the first day of at least 3 different days the ANC is measured as 500 / uL or greater

  6. Cross-sectional Analysis: Day of Recovery of Platelet Count to 20,000 / uL [ Time Frame: an expected average of 5 years ]
    Day of Recovery of Platelet Count to 20,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 20,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

  7. Cross-sectional Analysis: Day of Recovery of Platelet Count to 50,000 / uL [ Time Frame: an expected average of 5 years ]
    Day of Recovery of Platelet Count to 50,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 50,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.


Secondary Outcome Measures :
  1. Longitudinal Analysis: Proportion of Participants Achieving Hematologic Reconstitution [ Time Frame: an expected average of 5 years ]

    Hematologic Reconstitution is defined as attainment of each of the following lab test values:

    • Hemoglobin within normal range for age
    • WBC count within normal range for age
    • Absolute neutrophil count (ANC) within normal range for age
    • Platelet count ≥ 150,000/microL and without transfusion for at least 7 consecutive days

  2. Longitudinal Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL [ Time Frame: an expected average of 5 years ]
    Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL is defined as the first day of at least 3 different days the ANC is measured as 500 / uL or greater.

  3. Longitudinal Analysis: Day of Recovery of Platelet Count to 20,000 / uL [ Time Frame: an expected average of 5 years ]
    Day of Recovery of Platelet Count to 20,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 20,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

  4. Longitudinal Analysis: Day of Recovery of Platelet Count to 50,000 / uL [ Time Frame: an expected average of 5 years ]
    Day of Recovery of Platelet Count to 50,000 / uL is defined as the first day of at least 3 laboratory values obtained on different days where the platelet count was measured as 50,000 / uL or greater, AND without platelet transfusions for at least 7 consecutive days immediately preceding this day.

  5. Longitudinal Analysis: Proportion of Participants Achieving Full T Cell Immune Reconstitution [ Time Frame: an expected average of 5 years ]
    • Absolute CD3 T cell count within normal range for age
    • Absolute CD4 T cell count within normal range for age
    • Absolute CD8 T cell count within normal range for age
    • Proliferative responses to PHA within the normal range (at or above the lower limit of normal).
    • When possible the proliferation to PHA should be calculated as a percentage of the lower limit of normal controls for that laboratory; alternatively, the lower limit of normal controls for the day may be used.

  6. Longitudinal Analysis: Proportion of Participants Achieving Full B Cell Immune Reconstitution [ Time Frame: an expected average of 5 years ]
    • Quantitative immunoglobulins (IgG, IgM, and IgA) within normal range for age; each immunoglobulin level will be assessed separately.
    • Serologic confirmation of post immunization tetanus titer in protective range.
    • Serologic confirmation of post immunization pneumococcal titers in protective range (protective titers for > 50% of the serotypes contained in the vaccine) following immunization.
    • Patients who remain on IVIG will be considered not B cell reconstituted.
    • Normalization of isohemagglutinin titers.

  7. Longitudinal Analysis: State of Lineage Specific Chimerism (HCT Stratum) [ Time Frame: an expected average of 5 years ]
    Peripheral blood chimerism will be assessed by FISH XX/XY, STRs, or WASP expression.

  8. Longitudinal Analysis: Definition of Graft Failure / Rejection [ Time Frame: an expected average of 5 years ]
    • Less than 5% of donor cells in all lineages or in whole blood by 100 days post-HCT using standard PCR based or in situ hybridization techniques OR
    • Second transplant by 100 days post-HCT (unless > 5% CD3 and purpose is to boost immune recovery).

    Failure to achieve ≥5% donor cells in all lineages or in whole blood by 100 days post-HCT will be defined as graft failure/rejection. Patients who receive a second transplant by day 100 will be considered graft failure.


  9. Longitudinal Analysis: Severe bleeding episodes [ Time Frame: an expected average of 5 years ]
    Any severe bleeding episode requiring platelet and/or RBC transfusion(s)

  10. Longitudinal Analysis: Malignancy [ Time Frame: an expected average of 5 years ]
    New onset or relapse of lymphoid malignancy confirmed by relevant pathologic and genetic features.

  11. Longitudinal Analysis: Growth [ Time Frame: an expected average of 5 years ]
    Z score of weight and height pre-HCT/gene therapy and post-HCT/gene therapy.

  12. Longitudinal Analysis: Incidence of Acute GVHD [ Time Frame: an expected average of 5 years ]
    The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the Consensus criteria of Grades IIIV or grades III-IV acute GVHD1 are considered events. Death is a competing risk, and patients alive without acute GVHD will be censored at the time of last follow-up.

  13. Longitudinal Analysis: Incidence of Chronic GVHD [ Time Frame: an expected average of 5 years ]
    Chronic GVHD will be graded as limited or extensive.2 Occurrence of symptoms in any organ system that meet the criteria of chronic GVHD will be recorded. Death is a competing risk, and patients alive without chronic GVHD will be censored at time of last follow-up.

  14. Longitudinal Analysis: Autoimmunity disorders [ Time Frame: an expected average of 5 years ]
    Incidence of documented autoimmunity disorders

  15. Longitudinal Analysis: Infections / blood borne infections [ Time Frame: an expected average of 5 years ]
    1. Clinical resolution of any pre-HCT opportunistic infections including but not limited to CMV, HSV1, adenovirus, EBV, and VZV. Approximate time to resolution (clinically well, off treatment, and/or negative culture/PCR assay) will be measured from the day of HCT.
    2. Incidence of documented severe (requiring hospitalization or resulting in death) and/or recurrent bacterial, viral or fungal infection post HCT. These will be reported by site of disease, organism, date of onset post HCT, and whether or not the infection resolved.
    3. Presence and resolution of severe warts (verruca vulgaris, flat warts) from the day of HCT. Whether the subject had complete resolution, partial resolution, persistent or recurrent warts will be recorded.
    4. New episodes of infections due to meningococcus, pneumococcus or hemophilus.
    5. Lymphoproliferative disease due to EBV.

  16. Cross-sectional Analysis: Current State of Lineage Specific Chimerism (HCT Stratum) [ Time Frame: an expected average of 5 years ]
    Peripheral blood donor chimerism will be assessed by FISH XX/XY, STR, and/or WASP expression

  17. Cross-sectional Analysis: Current frequency and severity of infections [ Time Frame: an expected average of 5 years ]
  18. Cross-sectional Analysis: Current Status of Growth [ Time Frame: an expected average of 5 years ]
    Current Z score of weight and height pre-HCT/gene therapy and post-HCT/gene therapy.

  19. Cross-Sectional Analysis: Graft-versus-host Disease (GvHD) [ Time Frame: an expected average of 5 years ]
    Presence of chronic GVHD, current assessment; graded as limited or extensive

  20. Cross-Sectional Analysis: Autoimmunity Disorders [ Time Frame: an expected average of 5 years ]
    Presence of autoimmunity disorders

  21. Cross-sectional Analysis: Severe Bleeding Episodes [ Time Frame: an expected average of 5 years ]
    Any severe bleeding episode requiring platelet and/or RBC transfusion(s) during the previous year.

  22. Cross-sectional Analysis: fertility [ Time Frame: an expected average of 5 years ]
    Whether the subject has biological offspring will be recorded.

  23. Cross-sectional Analysis: malignancy [ Time Frame: an expected average of 5 years ]
    New onset or relapse of lymphoid malignancy confirmed by relevant pathologic and genetic features.

  24. Cross-sectional Analysis: Quality of Life Questionnaire [ Time Frame: an expected average of 5 years ]
    Age appropriate testing will be performed at the cross-sectional visit inpatients surviving at least two years post-transplant


Biospecimen Retention:   Samples With DNA
Whole blood and tissue samples


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Male WAS participants treated at consortium centers Since 1990
Criteria

Inclusion Criteria:

  • WAS participants will be defined as males who have:

    1. thrombocytopenia (< 100K) AND EITHER molecular diagnosis of WAS OR reduced WASP expression; OR
    2. thrombocytopenia (< 100K) AND positive family history consistent with WAS diagnosis; OR
    3. chronic thrombocytopenia (< 100K for minimum of 3 months) AND low mean platelet volume (MPV below normal range for age) AND EITHER recurrent and/or severe infections requiring treatment and/or eczema OR lack of antibody response to polysaccharide antigens or low IgM.
  • Longitudinal Analysis (Retrospective and Prospective)

    1. Stratum A. Participants with WAS who have or will Receive HCT

      • Participants with WAS who have received an HCT since January 1, 1990
    2. Stratum B. Participants with WAS who have or will Receive Gene Transfer

      • Participants in which the intention is to treat with gene transfer with autologous modified cells
  • Cross-Sectional Analysis (Strata A and B) 1. Participants with WAS who are surviving and at least 2 years after the most recent HCT or gene therapy.

Exclusion Criteria:

  • As this is a natural history study, for both the Longitudinal Analysis and the Cross-Sectional Analysis we will not exclude any patients due to race or age who fit the inclusion criteria.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02064933


  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
UCLA
Los Angeles, California, United States, 90095-1752
Lucile Salter Packard Children's Hospital at Stanford
Palo Alto, California, United States, 94304
UCSF Benioff Children's Hospital
San Francisco, California, United States, 94143-1278
United States, Colorado
Children's Hospital Denver
Denver, Colorado, United States, 80220
United States, Delaware
Alfred I. duPont Hospital for Children/Nemours
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center, Washington DC
Washington, District of Columbia, United States, 20010-2970
United States, Florida
Johns Hopkins All Children's Hospital - St. Petersburg, FL
Saint Petersburg, Florida, United States, 33701
United States, Georgia
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60614
United States, Louisiana
Children's Hospital of New Orleans at LSUHSC
New Orleans, Louisiana, United States, 70118
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota Medical Center
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Hospital
Rochester, Minnesota, United States, 55905
United States, Missouri
Cardinal Glennon Children's Hospital/ St. Louis University
Saint Louis, Missouri, United States, 63104
Washington University/ St.Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan-kettering Cancer Center
New York, New York, United States, 10065
University of Rochester Medical Center/ Golisano Children's Hospital
Rochester, New York, United States, 14642
New York Medical College, Maria Fareri Children's Hospital
Valhalla, New York, United States, 10595
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Rainbow Babies/ University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390-9263
Baylor College of Medicine/ Texas Children's Hospital
Houston, Texas, United States, 77030-2399
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
United States, Utah
Primary Children's Medical Center/ University of Utah
Salt Lake City, Utah, United States, 84113
United States, Washington
Fred Hutchinson Cancer Research Center/ Seattle Children's
Seattle, Washington, United States, 98109
United States, Wisconsin
University of Wisconsin/ American Family Children's Hospital
Madison, Wisconsin, United States, 53705-2275
Children's Hospital of Wisconsin-Milwaukee
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
Cancer Care Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1XB
Canada, Quebec
CHU St. Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Primary Immune Deficiency Treatment Consortium (PIDTC)
Rare Diseases Clinical Research Network
Investigators
Principal Investigator: Lauri M Burroughs, MD University of Washington

Additional Information:
Publications of Results:

Other Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02064933     History of Changes
Other Study ID Numbers: DAIT RDCRN PIDTC-6904
First Posted: February 17, 2014    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Wiskott-Aldrich Syndrome
Hematopoietic Stem Cell Transplantation
Genetic Therapy

Additional relevant MeSH terms:
Wiskott-Aldrich Syndrome
Syndrome
Disease
Pathologic Processes
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphopenia
Leukopenia
Leukocyte Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Immunologic Deficiency Syndromes
Immune System Diseases