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NCT Number: NCT04528355

Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With 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.

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Key information

Conditions

Primary Immunodeficiency (PID) Adrenal Gland Diseases Adrenal Insufficiency Adrenoleukodystrophy Albinism Anemia Anemia, Aplastic Anemia, Diamond-Blackfan Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Hypoplastic, Congenital Anemia, Sickle Cell Arthritis Arthritis, Rheumatoid Autoimmune Diseases Autoimmune Lymphoproliferative Syndrome Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Blood Protein Disorders Bone Diseases Bone Diseases, Developmental Bone Marrow Diseases Bone Marrow Failure Disorders Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Carbohydrate Metabolism, Inborn Errors Central Nervous System Diseases Chediak-Higashi Syndrome Chronic Disease Congenital Bone Marrow Failure Syndromes Congenital amegakaryocytic thrombocytopenia Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Crohn Disease Cytopenia DNA Repair-Deficiency Disorders Death Death, Sudden Demyelinating Diseases Digestive System Diseases Disease Disease Attributes Dysgammaglobulinemia Endocrine System Diseases Eye Diseases Eye Diseases, Hereditary Gastroenteritis Gastrointestinal Diseases Gaucher Disease Genetic Diseases, Inborn Genetic Diseases, X-Linked Granulomatous Disease, Chronic Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Hemorrhagic Disorders Hereditary Anemias Hereditary Central Nervous System Demyelinating Diseases Heredodegenerative Disorders, Nervous System Histiocytosis Histiocytosis, Non-Langerhans-Cell Hyper-IgM Immunodeficiency Syndrome Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome Immune System Diseases Immunologic Deficiency Syndromes Immunoproliferative Disorders Infant Death Infant, Newborn, Diseases Inflammatory Bowel Diseases Inflammatory Conditions Inherited Metabolic Disorders (IMD) Intellectual Disability Intestinal Diseases Joint Diseases Leukocyte Disorders Leukocyte adhesion deficiency type 1 Leukodystrophy, Globoid Cell Leukodystrophy, Metachromatic Leukoencephalopathies Leukopenia Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lymphatic Diseases Lymphohistiocytosis, Hemophagocytic Lymphopenia Lymphoproliferative Disorders Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Mannosidase Deficiency Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis I Musculoskeletal Diseases Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Nutritional and Metabolic Diseases Osteochondrodysplasias Osteopetrosis Osteosclerosis Pathologic Processes Pathological Conditions, Signs and Symptoms Peroxisomal Disorders Phagocyte Bactericidal Dysfunction Primary Immunodeficiency Diseases Red-Cell Aplasia, Pure Rheumatic Diseases Severe Combined Immunodeficiency Skin and Connective Tissue Diseases Sphingolipidoses Sudden Infant Death Sulfatidosis Syndrome Thalassemia Wiskott-Aldrich Syndrome X-Linked Intellectual Disability alpha-Mannosidosis beta-Thalassemia

Age range

2 month–60 year

Sex eligibility

All sexes

Study type

Observational

Primary location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location status: Recruiting

Location contact

Craig Byersdorfer, MD

SUB_INVESTIGATOR

Elizabeth Stenger, MD

SUB_INVESTIGATOR

Jessie Barnum, MD

SUB_INVESTIGATOR

Maria Escolar, MD

SUB_INVESTIGATOR

Randy Windreich, MD

SUB_INVESTIGATOR

Shawna McIntyre, RN

CONTACT

[email protected]

412-692-5552

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Treatment and study plan

data collection

Drug

Study subjects will receive alemtuzumab, melphalan, thiotepa, fludarabine and hydroxyurea-based, reduced-intensity conditioning regimen in accordance with clinical practice at UPMC Children's Hospital of Pittsburgh at the discretion of the treating physician. Medical data will be abstracted from subject's medical charts once the patient signs the informed consent.

Primary outcomes

  1. incidence of acute graft versus host disease (GVHD)

    Time frame: up to 5 years

    grades 3-4, chronic extensive GVHD

  2. overall survival after HSCT

    Time frame: up to 5 years

    review of the existing medical records to check on the participant's survival status

Secondary outcomes

  1. Describe degree of engraftment, based upon chimerism data

    Time frame: up to 5 years

    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

  2. Describe probability to discontinue systemic immunosuppression medications

    Time frame: by 6, 9, and 12 months post-HSCT

    review of the existing medical records to check on the participant's current medications

  3. Describe the tempo of immune reconstitution

    Time frame: over the first year post transplant

    review of the various test results in existing medical records to check on the participant's immune system recovery rate

  4. Describe the use of donor leukocyte infusion (DLI)

    Time frame: up to 5 years

    review of the existing medical records to check on the participant's need for DLI

Study contacts

Contact information is provided by the study sponsor or research team.

Paul Szabolcs, MD

CONTACT

[email protected]

412-692-5427

Shawna McIntyre, RN

CONTACT

[email protected]

412-692-5552

Sponsors and collaborators

Lead sponsor

Paul Szabolcs

Other

Registry information

Official study title

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)

Acronym: PRO-RIC

Important dates

Study start
2020
Primary completion
2027
Study completion
2028
First posted
Aug 27, 2020
Registry last updated
Jan 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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