Natural History Study of SCID Disorders

Individuals with a recent or new diagnosis of severe combined immune deficiency (including infants who were identified by newborn screening) may be eligible to be enrolled on the PIDTC research study 6901. Speak to your doctor to determine if you or your child may be eligible. Protocol 6901 follows patients with SCID prospectively, meaning the 6901 study enrolls participants where there is a plan to receive a blood and marrow transplant, enzyme therapy, or gene therapy in the future. Patients are then followed according to a schedule set out by the study protocol after the procedure. The times the study requests follow up will be the same as when your doctor would want to be seeing you or your child as part of their regular ongoing medical care. Patients with "leaky SCID", reticular dysgenesis, and Omenn syndrome may also be eligible to participate in 6901. The 6901 research study does NOT dictate how your or your child's doctors should treat you or your child, as the PIDTC recognizes that there are many complex factors that go into this decision. The decision about how you or your child with SCID will be treated is made by your doctor. The 6901 study simply follows how you or your child do over time. There are no experimental therapies on this study. The 6901 study has been open since August 2010, and continues to be open and enrolling patients to the present day. The study plans to enroll approximately 250 patients with SCID. By studying new patients undergoing treatment for SCID, the goal is to learn more about: (1) outcomes from the treatment of SCID in the modern era of medicine, (2) what factors lead to the best long-term outcomes, such as best donor, conditioning regimen, timing of transplant, etc. and (3) what impact newborn screening and the early diagnosis of SCID has had on the long-term outcomes following BMT or gene therapy. A significant amount of information is also being gathered on how and when the immune system recovers after BMT, quality of life for long-term survivors, and about whether children develop normally after treatment. The 6901 study is the largest coordinated prospective study of patients with SCID ever performed. Information that we will learn, both now and in the future, will help doctors and other health professionals to better treat children with SCID. All hospitals within the PIDTC are enrolling patients with SCID on 6901, ensuring that the outcomes are reflective of what happens in the "real world" as opposed to at just one or two large centers. ]]>
PIDTC 6901 18, 30 and 42 Month Post Hematopoietic Cell Transplantation (HCT) ChecklistPIDTC 6901 6 Month Post Hematopoietic Cell Transplantation (HCT) ChecklistPIDTC 6901 6 Month Post Hematopoietic Cell Transplantation (HCT) Evaluation WorksheetDemographics (Short)PIDTC 6901 Day 100 Post Hematopoietic Cell Transplantation (HCT) WorksheetPIDTC 6901 12, 24, 36 and 48 Month Post Hematopoietic Cell Transplantation (HCT) Evaluation WorksheetPIDTC 6901 12 and 24 Month Post Hematopoietic Cell Transplantation (HCT) ChecklistPIDTC 6901 36 Month Post Hematopoietic Cell Transplantation (HCT) ChecklistPIDTC 6901 48 Month Post Hematopoietic Cell Transplantation (HCT) ChecklistPIDTC 6901 Pre-Initiation for Hematopoietic Cell Transplantation (HCT) Baseline ChecklistPIDTC 6901 Baseline Assessment - Pre-Initiation of Conditioning for Hematopoietic Cell Transplantation (HCT) WorksheetPIDTC 6901 Day 0 - Hematopoietic Cell Transplantation (HCT) ChecklistPIDTC 6901 Day 100 Post Hematopoietic Cell Transplantation (HCT) ChecklistPIDTC 6901 Patient Eligibility and Stratum Assignment Version 3.0PIDTC 6901 Patient Eligibility and Stratum Assignment Version 2.0PIDTC: PROTOCOL DEVIATION/VIOLATION REPORT FORMPIDTC 6901 SCID Early Life (Pre-Diagnosis) Assessment FormPIDTC 6901 Treatment Assessment WorksheetPIDTC: PROTOCOL DEVIATION/VIOLATION REPORT FORMPIDTC 6901 DAY 0 / TREATMENT DESCRIPTION: PROTOCOL INFORMATION AND PREPARATIVE REGIMENPIDTC 6901 SUBSEQUENT DISEASE TREATMENT (HCT, ERT OR GT) – DATE AND LOCATIONPIDTC 6901 TREATMENT AT THIS VISIT DATEPIDTC 6901 TREATMENT AT THIS VISIT DATEPIDTC 6901 DAY 0 / TREATMENT DESCRIPTION: GENE THERAPY CELLULAR TARGET, VECTOR AND INFUSION PRODUCTPIDTC 6901 ERT TESTINGPIDTC 6901 SUBSEQUENT DISEASE TREATMENT (HCT, ERT OR GT) – METABOLIC TESTINGChimerism StudiesPatients who meet the following inclusion criteria and the intention is to treat with allogeneic hematopoietic cell transplant (HCT) are eligible for enrollment into Stratum A (Classic SCID) of the study: Absence or very low number of T cells (CD3 T cells < 300/microliter), AND no or very low T cell function (< 10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA) OR T cells of maternal origin present Note #1: When possible the proliferation to PHA should be calculated as a percentage of the lower limit of normal controls for that laboratory. If a range is not available, patients with stimulation index (SI) < 10 or whose absolute cpms are <10% of the cpms of the normal control of the day are eligible. SI = (cpm of subject - cpm of medium) / cpm of medium Note #2: For patients with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion. Patients who meet the following criteria and the intention is to treat with HCT are eligible for enrollment into Stratum B (Omenn/Leaky SCID/Reticular Dysgenesis) of the study: Leaky SCID Maternal lymphocytes not detected, AND either one or both of the following with rule-out of MHC Class I and II non-expression by flow cytometry (or histology): < 30% of lower limit of normal T cell function (as measured by response to PHA), Absent or less than 10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (post vaccination or exposure), with expression of HLA by flow/serology AND either one or both of the following: > 80% of CD3+ or CD4 T cells are CD45RO+ (< 2 years of age) Genetic abnormality for SCID AND does not meet criteria for Omenn Syndrome Note: For patients with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion. Omenn Syndrome (OS) Generalized skin rash Maternal lymphocytes not detected IF: Maternal engraftment was not assessed and ruled out, the patient is not eligible as Omenn Syndrome. > 80% of CD3 or CD4 T cells are CD45RO+ ( < 2 years of age) Absent or low (< 30% lower limit of normal) T cell proliferation to antigens IF: Proliferation to antigen was not performed, but at least 4 of the following 8 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the patient is eligible as Omenn Syndrome. Hepatomegaly Splenomegaly Lymphadenopathy Elevated IgE Elevated absolute eosinophil count *Oligoclonal T cells measured by CDR3 length or flow cytometry *Proliferation to PHA is reduced <30% of lower limit of normal or SI < 20 *Mutation to SCID causing gene Reticular Dysgenesis (RD) < 300 / ul T cell number None or < 10% lower limit of normal PHA proliferation Severe neutropenia (< 200 / uL) AND one or more of the following: Sensori-neural deafness OR Deficiency of marrow granulopoiesis OR A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified. Note: Lack of response to short-term G-CSF administration can be used as a diagnostic criterion, however, long-term administration is not recommended. Patients who meet the following criteria and the intention is to treat with PEG-ADA ERT or gene therapy with autologous modified (gene transduced) cells are eligible for enrollment into Stratum C: ADA Deficient SCID with intention to treat with PEG-ADA ERT ADA Deficient SCID with intention to treat with gene therapy X-linked SCID with intention to treat with gene therapy Note: For patients with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion. Patients who meet any one or more of the following exclusion criteria are disqualified from enrollment in Strata A, B, or C of the study. Subjects will be excluded as defined by: Presence of an HIV infection (by PCR) or other cause of secondary immunodeficiency. Presence of DiGeorge syndrome unless SCID genotype is also present. Most patients with defects insuch as nucleoside phosphorylase, ZAP70, CD40 ligand, NEMO, XLP, RMP, DOCK8, MST1, ORAI1, STIM1, CORO1A MAGT1, IKBA, or RHOH will not meet the inclusion criteria for Stratum A, B, or C above. However, a patient with one of the above may meet the inclusion criteria for Stratum A or Stratum B and if so will be included. Version 3.0 28 August 2012 MHC Class I and MHC Class II antigen deficiency are specifically excluded. Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency, transcobalamin deficiency. ]]>
Study Activated August 19, 2010 First Accrual September 2, 2010 ]]>