Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With RIC (PRO-RIC)

A Prospective Outcomes Study of Pediatric and Adult Patients With Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation With a Reduced-Intensity Conditioning Regimen (PRO-RIC)

This is a data collection study that will examine the general diagnostic and treatment data associated with the reduced-intensity chemotherapy-based regimen paired with simple alemtuzumab dosing strata designed to prevented graft failure and to aid in immune reconstitution following hematopoietic stem cell transplantation.

Study Overview

• Status: Recruiting
• Conditions: Congenital Bone Marrow Failure Syndromes; Inflammatory Conditions; Primary Immunodeficiency (PID); Inherited Metabolic Disorders (IMD); Hereditary Anemias
• Intervention / Treatment: Drug: data collection

Detailed Description

Hematopoietic stem cell transplantation (HSCT) from a healthy donor can cure or alleviate a broad spectrum of non-malignant disorders (NMD). Although reduced-intensity conditioning (RIC) regimens promise decreased treatment-related morbidity and mortality, graft failure and infections are limiting the use of RIC in chemotherapy-naive patients. Dr. Szabolcs have completed several trials to evaluate a novel RIC regimen of alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa. The last trial at UPMC Children's Hospital of Pittsburgh of a highly effective and biologically rational chemotherapy-based RIC regimen paired with simple alemtuzumab dosing strata was tested and resulted in outstanding survival and remarkably low rates of graft failure. The favorable outcome described may serve as a toxicity and efficacy reference for emerging gene therapy strategies as well.

This prospective collection of clinical data will allow the investigators to further assess engraftment, GVHD, immunosuppressant use and overall survival in this patient population.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Shawna McIntyre, RN; Phone Number: 412-692-5552; Email: mcintyresm@upmc.edu
• Study Contact Backup: Name: Paul Szabolcs, MD; Phone Number: 412-692-5427; Email: paul.szabolcs@chp.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • UPMC Children's Hospital of Pittsburgh
      • Contact: Shawna McIntyre, RN; Phone Number: 412-692-5552; Email: mcintyresm@upmc.edu
      • Sub-Investigator: Jessie Barnum, MD
      • Sub-Investigator: Maria Escolar, MD
      • Sub-Investigator: Randy Windreich, MD
      • Sub-Investigator: Craig Byersdorfer, MD
      • Sub-Investigator: Elizabeth Stenger, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients with Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation

Description

Inclusion Criteria:

1. Patient, parent, or legal guardian must have given written informed consent.
2. Patient must be 2 months to 60 years (inclusive) of age at time of consent for all diagnoses.

3. Patients should have a non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to the following:

   A. Primary Immunodeficiency Syndromes

   • Severe Combined Immune Deficiency (SCID) with NK cell activity
   • Omenn Syndrome
   • Bare Lymphocyte Syndrome (BLS)
   • Combined Immune Deficiency (CID) syndromes
   • Combined Variable Immune Deficiency (CVID) syndrome
   • Wiskott-Aldrich Syndrome
   • Leukocyte adhesion deficiency
   • Chronic granulomatous disease (CGD)
   • Hyper IgM (XHIM) syndrome
   • IPEX syndrome
   • Chediak-Higashi Syndrome
   • Autoimmune Lymphoproliferative Syndrome (ALPS)
   • Hemophagocytic Lymphohistiocytosis (HLH) syndromes
   • Lymphocyte Signaling defects

   B. Congenital Bone Marrow Failure Syndromes

   • Congenital Amegakaryocytic Thrombocytopenia (CAMT)
   • Osteopetrosis

   C. Inherited Metabolic Disorders (IMD)

   • Mucopolysaccharidoses

     • Hurler syndrome (MPS I)
     • Hunter syndrome (MPS II)

   • Leukodystrophies

     • Krabbe Disease, also known as globoid cell leukodystrophy
     • Metachromatic leukodystrophy (MLD)
     • X-linked adrenoleukodystrophy (ALD)

   • Other inherited metabolic disorders

     • Alpha Mannosidosis
     • Gaucher Disease
     • Other inheritable metabolic diseases where HSCT may be beneficial

   D. Hereditary Anemias

   • Thalassemia major
   • Sickle cell disease (SCD)
   • Diamond Blackfan Anemia (DBA)

   E. Inflammatory Conditions

   • Crohn's Disease or Inflammatory Bowel Disease
   • IPEX or IPEX-like Syndromes
   • Rheumatoid Arthritis
   • Other inflammatory conditions where HSCT may be beneficial
4. Subjects receive either umbilical cord blood, bone marrow, or peripheral blood stem cell transplant with an alemtuzumab, melphalan, thiotepa, fludarabine and hydroxyurea-based, reduced-intensity conditioning regimen, according to clinical practice at UPMC Children's Hospital of Pittsburgh.

There are no exclusion criteria.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of acute graft versus host disease (GVHD)	grades 3-4, chronic extensive GVHD	up to 5 years
overall survival after HSCT	review of the existing medical records to check on the participant's survival status	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe degree of engraftment, based upon chimerism data	review of chimerism test results in the existing medical records to check on degree of donor engraftment measured by the percentage of donor-derived blood cells in the HSCT recipient	up to 5 years
Describe probability to discontinue systemic immunosuppression medications	review of the existing medical records to check on the participant's current medications	by 6, 9, and 12 months post-HSCT
Describe the tempo of immune reconstitution	review of the various test results in existing medical records to check on the participant's immune system recovery rate	over the first year post transplant
Describe the use of donor leukocyte infusion (DLI)	review of the existing medical records to check on the participant's need for DLI	up to 5 years

Collaborators and Investigators

• Sponsor: Paul Szabolcs
• Investigators: Principal Investigator: Paul Szabolcs, MD, UPMC Children's Hospital of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Inflammatory Bowel Disease; Crohn's Disease; Gaucher Disease; Osteopetrosis; Omenn Syndrome; Bare Lymphocyte Syndrome (BLS); Combined Immune Deficiency (CID) syndromes; Wiskott-Aldrich Syndrome; Leukocyte adhesion deficiency; Chronic granulomatous disease (CGD); IPEX syndrome; Autoimmune Lymphoproliferative Syndrome (ALPS); Hemophagocytic Lymphohistiocytosis (HLH) syndromes; Lymphocyte Signaling defects; Congenital Amegakaryocytic Thrombocytopenia (CAMT); Hurler syndrome (MPS I); Metachromatic leukodystrophy (MLD); X-linked adrenoleukodystrophy (ALD); Thalassemia major; Sickle cell disease (SCD); Diamond Blackfan Anemia (DBA); Severe Combined Immune Deficiency (SCID) with NK cell activity; Hyper IgM (XHIM) syndrome; Chediak-Higashi Syndrome; Hurler syndrome (MPS II); Krabbe Disease, also known as Globoid Cell Leukodystrophy; Alpha Mannosidosis; IPEX or IPEX-like Syndromes
• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Cytopenia; Neurologic Manifestations; Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Arthritis; Joint Diseases; Rheumatic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Intestinal Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Disease; Digestive System Diseases; Gastrointestinal Diseases; Neurobehavioral Manifestations; Infant, Newborn, Diseases; Death; Eye Diseases; Leukocyte Disorders; Hematologic Diseases; Demyelinating Diseases; Immunologic Deficiency Syndromes; Gastroenteritis; Eye Diseases, Hereditary; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Blood Coagulation Disorders; Bone Marrow Diseases; Heredodegenerative Disorders, Nervous System; Lipid Metabolism Disorders; Adrenal Gland Diseases; Blood Protein Disorders; Hemorrhagic Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Intellectual Disability; Genetic Diseases, X-Linked; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Blood Coagulation Disorders, Inherited; Leukopenia; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Lipid Metabolism, Inborn Errors; DNA Repair-Deficiency Disorders; Phagocyte Bactericidal Dysfunction; Death, Sudden; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Lysosomal Storage Diseases, Nervous System; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Albinism; Anemia, Hypoplastic, Congenital; Red-Cell Aplasia, Pure; Sphingolipidoses; Lipidoses; Anemia, Aplastic; Mucopolysaccharidoses; Dysgammaglobulinemia; Adrenal Insufficiency; Sulfatidosis; Thalassemia; Lymphopenia; Peroxisomal Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; X-Linked Intellectual Disability; Mannosidase Deficiency Diseases; Infant Death; Primary Immunodeficiency Diseases; Congenital Bone Marrow Failure Syndromes; Syndrome; Anemia, Sickle Cell; Crohn Disease; beta-Thalassemia; Arthritis, Rheumatoid; Severe Combined Immunodeficiency; Granulomatous Disease, Chronic; Mucopolysaccharidosis I; Osteopetrosis; Inflammatory Bowel Diseases; Anemia, Diamond-Blackfan; Lymphohistiocytosis, Hemophagocytic; Gaucher Disease; Hyper-IgM Immunodeficiency Syndrome; Adrenoleukodystrophy; Leukodystrophy, Metachromatic; Leukodystrophy, Globoid Cell; alpha-Mannosidosis; Chediak-Higashi Syndrome; Wiskott-Aldrich Syndrome; Autoimmune Lymphoproliferative Syndrome; Sudden Infant Death; Congenital amegakaryocytic thrombocytopenia; Leukocyte adhesion deficiency type 1; Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Data Collection
• Other Study ID Numbers: STUDY20070105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No