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

Wiskott-Aldrich Syndrome Clinical Trial

Official title:

Analysis of Patients Treated for Wiskott-Aldrich Syndrome Since January 1, 1990 (RDCRN PIDTC-6904)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02064933
• Other study ID #: DAIT RDCRN PIDTC-6904
• Status: Completed
• Start date: February 2, 2014
• Est. completion date: May 1, 2019

Study information

• Verified date: August 2020
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: May 1, 2019
• Est. primary completion date: May 1, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Syndrome
• Wiskott-Aldrich Syndrome

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	CHU Sainte-Justine, Department of Pediatrics, University of Montreal	Montreal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Health Centre of British Columbia	Vancouver	British Columbia
Canada	Cancer Care Manitoba, University of Manitoba	Winnipeg	Manitoba
United States	Department of Pediatrics, C. S. Mott Children's Hospital, University of Michigan	Ann Arbor	Michigan
United States	Aflac Cancer and Blood Disorders Center, Emory/Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Department of Pediatrics, University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center, University of Cincinnati	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Pediatrics, University of Texas Southwestern Medical Center	Dallas	Texas
United States	Children's Hospital Denver, University of Colorado	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Institute for Pediatric Cancer and Blood Disorders, Hackensack University Medical Center	Hackensack	New Jersey
United States	Baylor College of Medicine Section of Immunology, Allergy, and Retrovirology, Texas Children's Hospital	Houston	Texas
United States	Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California	Los Angeles	California
United States	Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles,	Los Angeles	California
United States	American Family Children's Hospital, University of Wisconsin	Madison	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Hospital of Wisconsin-Milwaukee	Milwaukee	Wisconsin
United States	Division of Pediatric Blood and Marrow Transplantation, University of Minnesota	Minneapolis	Minnesota
United States	Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University	New Orleans	Louisiana
United States	Department of Pediatrics, Memorial Sloan Kettering Cancer Center	New York	New York
United States	Lucile Salter Packard Children's Hospital at Stanford	Palo Alto	California
United States	Children's Hospital of Philadelphia, University of Pennsylvania	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	University of Pittsburgh Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Division of Pediatric Hematology/Oncology, Oregon Health and Science University	Portland	Oregon
United States	Department of Pediatrics, Golisano Children's Hospital, University of Rochester	Rochester	New York
United States	Mayo Clinic Children's Center	Rochester	Minnesota
United States	Cardinal Glennon Children's Hospital, Saint Louis University	Saint Louis	Missouri
United States	Saint Louis Children's Hospital, Washington University	Saint Louis	Missouri
United States	Blood and Marrow Transplant Program, Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Hospital, University of Utah	Salt Lake City	Utah
United States	Texas Transplant Institute, Methodist Children's Hospital	San Antonio	Texas
United States	University of California, San Francisco Benioff Children's Hospital	San Francisco	California
United States	Fred Hutchinson Cancer Research Center and University of Washington-Seattle Children's Hospital	Seattle	Washington
United States	Maria Fareri Children's Hospital, New York Medical College	Valhalla	New York
United States	Children's National Hospital-George Washington University School of Medicine and Health Sciences	Washington	District of Columbia
United States	Nemours Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Primary Immune Deficiency Treatment Consortium (PIDTC), Rare Diseases Clinical Research Network

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (9)

Burroughs LM, Petrovic A, Brazauskas R, Liu X, Griffith LM, Ochs HD, Bleesing JJ, Edwards S, Dvorak CC, Chaudhury S, Prockop SE, Quinones R, Goldman FD, Quigg TC, Chandrakasan S, Smith AR, Parikh S, Dávila Saldaña BJ, Thakar MS, Phelan R, Shenoy S, Forbes — View Citation

Dvorak CC, Cowan MJ, Logan BR, Notarangelo LD, Griffith LM, Puck JM, Kohn DB, Shearer WT, O'Reilly RJ, Fleisher TA, Pai SY, Hanson IC, Pulsipher MA, Fuleihan R, Filipovich A, Goldman F, Kapoor N, Small T, Smith A, Chan KW, Cuvelier G, Heimall J, Knutsen A — View Citation

Griffith LM, Cowan MJ, Kohn DB, Notarangelo LD, Puck JM, Schultz KR, Buckley RH, Eapen M, Kamani NR, O'Reilly RJ, Parkman R, Roifman CM, Sullivan KE, Filipovich AH, Fleisher TA, Shearer WT. Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: current status and critical needs. J Allergy Clin Immunol. 2008 Dec;122(6):1087-96. doi: 10.1016/j.jaci.2008.09.045. Epub 2008 Nov 6. — View Citation

Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fle — View Citation

Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, Burroughs LM, Torgerson TR, Decaluwe H, Haddad E; workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol. 2016 Aug;138(2):375-85. do — View Citation

Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, Conley ME, Fleisher TA, Gaspar HB, Kohn DB, Ochs HD, O'Reilly RJ, Rizzo JD, Roifman CM, Small TN, Shearer WT; Workshop Participants. Improving cellular therapy for primary immune defi — View Citation

Haddad E, Allakhverdi Z, Griffith LM, Cowan MJ, Notarangelo LD. Survey on retransplantation criteria for patients with severe combined immunodeficiency. J Allergy Clin Immunol. 2014 Feb;133(2):597-9. doi: 10.1016/j.jaci.2013.10.022. Epub 2013 Dec 10. — View Citation

Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Hanson IC, Filipovich AH, Jyonouchi S, Sullivan KE, Small TN, Burroughs L, Skoda-Smith S, Haight AE, Grizzle A, Pulsipher MA, Chan KW, Fuleihan RL, Haddad E, Loechelt B, Aquino VM — View Citation

Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, Griffith LM, Kohn DB, O'Reilly RJ, Fleisher TA, Pai SY, Martinez CA, Buckley RH, Cowan MJ. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Longitudinal Analysis: Overall Survival From Time of HCT/Gene Therapy	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.	an expected average of 5 years
Primary	Cross-Sectional Analysis: Proportion of Participants Achieving Full T Cell Reconstitution	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	an expected average of 5 years
Primary	Cross-Sectional Analysis: Proportion of Participants Achieving Full B Cell Reconstitution	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	an expected average of 5 years
Primary	Cross-Sectional Analysis: Proportion of Participants Achieving Resolution of thrombocytopenia	Resolution of thrombocytopenia defined by Platelets = 150,000/microliter (transfusion independent for at least 7 consecutive days)	an expected average of 5 years
Primary	Cross-Sectional Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL	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	an expected average of 5 years
Primary	Cross-sectional Analysis: Day of Recovery of Platelet Count to 20,000 / uL	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.	an expected average of 5 years
Primary	Cross-sectional Analysis: Day of Recovery of Platelet Count to 50,000 / uL	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: Proportion of Participants Achieving Hematologic Reconstitution	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	an expected average of 5 years
Secondary	Longitudinal Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: Day of Recovery of Platelet Count to 20,000 / uL	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: Day of Recovery of Platelet Count to 50,000 / uL	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: Proportion of Participants Achieving Full T Cell Immune Reconstitution	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: Proportion of Participants Achieving Full B Cell Immune Reconstitution	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: State of Lineage Specific Chimerism (HCT Stratum)	Peripheral blood chimerism will be assessed by FISH XX/XY, STRs, or WASP expression.	an expected average of 5 years
Secondary	Longitudinal Analysis: Definition of Graft Failure / Rejection	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: Severe bleeding episodes	Any severe bleeding episode requiring platelet and/or RBC transfusion(s)	an expected average of 5 years
Secondary	Longitudinal Analysis: Malignancy	New onset or relapse of lymphoid malignancy confirmed by relevant pathologic and genetic features.	an expected average of 5 years
Secondary	Longitudinal Analysis: Growth	Z score of weight and height pre-HCT/gene therapy and post-HCT/gene therapy.	an expected average of 5 years
Secondary	Longitudinal Analysis: Incidence of Acute GVHD	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: Incidence of Chronic GVHD	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.	an expected average of 5 years
Secondary	Longitudinal Analysis: Autoimmunity disorders	Incidence of documented autoimmunity disorders	an expected average of 5 years
Secondary	Longitudinal Analysis: Infections / blood borne infections	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.; 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.; 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.; New episodes of infections due to meningococcus, pneumococcus or hemophilus.; Lymphoproliferative disease due to EBV.	an expected average of 5 years
Secondary	Cross-sectional Analysis: Current State of Lineage Specific Chimerism (HCT Stratum)	Peripheral blood donor chimerism will be assessed by FISH XX/XY, STR, and/or WASP expression	an expected average of 5 years
Secondary	Cross-sectional Analysis: Current frequency and severity of infections		an expected average of 5 years
Secondary	Cross-sectional Analysis: Current Status of Growth	Current Z score of weight and height pre-HCT/gene therapy and post-HCT/gene therapy.	an expected average of 5 years
Secondary	Cross-Sectional Analysis: Graft-versus-host Disease (GvHD)	Presence of chronic GVHD, current assessment; graded as limited or extensive	an expected average of 5 years
Secondary	Cross-Sectional Analysis: Autoimmunity Disorders	Presence of autoimmunity disorders	an expected average of 5 years
Secondary	Cross-sectional Analysis: Severe Bleeding Episodes	Any severe bleeding episode requiring platelet and/or RBC transfusion(s) during the previous year.	an expected average of 5 years
Secondary	Cross-sectional Analysis: fertility	Whether the subject has biological offspring will be recorded.	an expected average of 5 years
Secondary	Cross-sectional Analysis: malignancy	New onset or relapse of lymphoid malignancy confirmed by relevant pathologic and genetic features.	an expected average of 5 years
Secondary	Cross-sectional Analysis: Quality of Life Questionnaire	Age appropriate testing will be performed at the cross-sectional visit inpatients surviving at least two years post-transplant	an expected average of 5 years

External Links

•   Division of Allergy, Immunology, and Transplantation (DAIT)
•   National Institute of Allergy and Infectious Diseases (NIAID)
•   Primary Immune Deficiency Treatment Consortium (PIDTC), Rare Clinical Diseases Research Network, National Institutes of Health