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

Paul Szabolcs

Status: Enrolling

Conditions: Inherited Metabolic Disorders (IMD); Primary Immunodeficiency (PID); Hereditary Anemias; Congenital Bone Marrow Failure Syndromes; Inflammatory Conditions

Treatments: Drug: data collection

Study type: Observational

Funder types: Other

Identifiers

NCT04528355

STUDY20070105

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 2 months to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.