Wiskott-Aldrich Syndrome Clinical Trial
Official title:
Analysis of Patients Treated for Wiskott-Aldrich Syndrome Since January 1, 1990 (RDCRN PIDTC-6904)
Verified date | August 2020 |
Source | National Institute of Allergy and Infectious Diseases (NIAID) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) | Primary Immune Deficiency Treatment Consortium (PIDTC), Rare Diseases Clinical Research Network |
United States, Canada,
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
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 |
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