Clinical trial NCT02064933: Patients Treated for Wiskott-Aldrich Syndrome (WAS) Since 1990
Official title: Analysis of Patients Treated for Wiskott-Aldrich Syndrome Since January 1, 1990 (RDCRN PIDTC-6904)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Wiskott-Aldrich Syndrome
Keywords: Wiskott-Aldrich Syndrome
Hematopoietic Stem Cell Transplantation
Genetic Therapy
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Primary Immune Deficiency Treatment Consortium (PIDTC)
name: Rare Diseases Clinical Research Network
First posted: 2014-02-17
Enrollment: 305
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male WAS participants treated at consortium centers Since 1990

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.


Eligibility 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.

Primary outcomes:
measure: Longitudinal Analysis: Overall Survival From Time of HCT/Gene Therapy
timeFrame: an expected average of 5 years
measure: Cross-Sectional Analysis: Proportion of Participants Achieving Full T Cell Reconstitution
timeFrame: an expected average of 5 years
measure: Cross-Sectional Analysis: Proportion of Participants Achieving Full B Cell Reconstitution
timeFrame: an expected average of 5 years
measure: Cross-Sectional Analysis: Proportion of Participants Achieving Resolution of thrombocytopenia
timeFrame: an expected average of 5 years
measure: Cross-Sectional Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: Day of Recovery of Platelet Count to 20,000 / uL
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: Day of Recovery of Platelet Count to 50,000 / uL
timeFrame: an expected average of 5 years
Secondary outcomes:
measure: Longitudinal Analysis: Proportion of Participants Achieving Hematologic Reconstitution
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Day of Recovery of Absolute Neutrophil Count (ANC) to 500 / uL
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Day of Recovery of Platelet Count to 20,000 / uL
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Day of Recovery of Platelet Count to 50,000 / uL
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Proportion of Participants Achieving Full T Cell Immune Reconstitution
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Proportion of Participants Achieving Full B Cell Immune Reconstitution
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: State of Lineage Specific Chimerism (HCT Stratum)
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Definition of Graft Failure / Rejection
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Severe bleeding episodes
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Malignancy
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Growth
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Incidence of Acute GVHD
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Incidence of Chronic GVHD
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Autoimmunity disorders
timeFrame: an expected average of 5 years
measure: Longitudinal Analysis: Infections / blood borne infections
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: Current State of Lineage Specific Chimerism (HCT Stratum)
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: Current frequency and severity of infections
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: Current Status of Growth
timeFrame: an expected average of 5 years
measure: Cross-Sectional Analysis: Graft-versus-host Disease (GvHD)
timeFrame: an expected average of 5 years
measure: Cross-Sectional Analysis: Autoimmunity Disorders
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: Severe Bleeding Episodes
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: fertility
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: malignancy
timeFrame: an expected average of 5 years
measure: Cross-sectional Analysis: Quality of Life Questionnaire
timeFrame: an expected average of 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Department of Pediatrics, University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California
state: California
city: Los Angeles
country: United States
facility: Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles,
state: California
city: Palo Alto
country: United States
facility: Lucile Salter Packard Children's Hospital at Stanford
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Benioff Children's Hospital
state: California
city: Denver
country: United States
facility: Children's Hospital Denver, University of Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours Alfred I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Hospital-George Washington University School of Medicine and Health Sciences
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Blood and Marrow Transplant Program, Johns Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Aflac Cancer and Blood Disorders Center, Emory/Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: New Orleans
country: United States
facility: Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University
state: Louisiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Department of Pediatrics, C. S. Mott Children's Hospital, University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Children's Center
state: Minnesota
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital, Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Children's Hospital, Washington University
state: Missouri
city: Hackensack
country: United States
facility: Institute for Pediatric Cancer and Blood Disorders, Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Department of Pediatrics, Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: Department of Pediatrics, Golisano Children's Hospital, University of Rochester
state: New York
city: Valhalla
country: United States
facility: Maria Fareri Children's Hospital, New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center, University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Division of Pediatric Hematology/Oncology, Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia, University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Pediatrics, University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Section of Immunology, Allergy, and Retrovirology, Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute, Methodist Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital, University of Utah
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center and University of Washington-Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: American Family Children's Hospital, University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin-Milwaukee
state: Wisconsin
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Children's & Women's Health Centre of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba, University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine, Department of Pediatrics, University of Montreal
state: Quebec
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Lauri M. Burroughs, MD
role: STUDY_CHAIR
affiliation: Department of Pediatrics, University of Washington-Seattle Children's Hospital
name: David J. Rawlings, MD
role: STUDY_CHAIR
affiliation: National Institute of Allergy and Infectious Diseases, NIH
name: Luigi D. Notarangelo, MD
role: STUDY_CHAIR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Alexandra H. Filipovich, MD
role: STUDY_CHAIR
References:
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.
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, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC; workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol. 2014 Feb;133(2):335-47. doi: 10.1016/j.jaci.2013.07.052. Epub 2013 Oct 15.
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. doi: 10.1016/j.jaci.2016.01.051. Epub 2016 Apr 22.
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, Gillio A, Davis J, Knutsen A, Smith AR, Moore TB, Schroeder ML, Goldman FD, Connelly JA, Porteus MH, Xiang Q, Shearer WT, Fleisher TA, Kohn DB, Puck JM, Notarangelo LD, Cowan MJ, O'Reilly RJ. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014 Jul 31;371(5):434-46. doi: 10.1056/NEJMoa1401177.
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. No abstract available.
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, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol. 2014 Apr;133(4):1092-8. doi: 10.1016/j.jaci.2013.09.044. Epub 2013 Nov 28.
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, Loechelt B, Moore T, Buckley RH. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. J Clin Immunol. 2013 Oct;33(7):1156-64. doi: 10.1007/s10875-013-9917-y. Epub 2013 Jul 2.
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 deficiency diseases: recognition, diagnosis, and management. J Allergy Clin Immunol. 2009 Dec;124(6):1152-60.e12. doi: 10.1016/j.jaci.2009.10.022.
citation: 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, Davila Saldana BJ, Thakar MS, Phelan R, Shenoy S, Forbes LR, Martinez C, Chellapandian D, Shereck E, Miller HK, Kapoor N, Barnum JL, Chong H, Shyr DC, Chen K, Abu-Arja R, Shah AJ, Weinacht KG, Moore TB, Joshi A, DeSantes KB, Gillio AP, Cuvelier GDE, Keller MD, Rozmus J, Torgerson T, Pulsipher MA, Haddad E, Sullivan KE, Logan BR, Kohn DB, Puck JM, Notarangelo LD, Pai SY, Rawlings DJ, Cowan MJ. Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report. Blood. 2020 Jun 4;135(23):2094-2105. doi: 10.1182/blood.2019002939.