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

study id #: NCT04528355

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

status: Recruiting

purpose:

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.

intervention: data collection

results: https://clinicaltrials.gov/ct2/show/results/NCT04528355

last updated: February 26, 2022

start date: August 20, 2020

estimated completion: June 30, 2026

last updated: September 21, 2021

size / enrollment: 50

study 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.

primary outcomes:

• 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 outcomes:

• Describe degree of engraftment, based upon chimerism data
  up to 5 years
• Describe probability to discontinue systemic immunosuppression medications
  by 6, 9, and 12 months post-HSCT
• Describe the tempo of immune reconstitution
  over the first year post transplant
• Describe the use of donor leukocyte infusion (DLI)
  up to 5 years

inclusion criteria:

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.

sponsor: Paul Szabolcs

contacts: Paul Szabolcs, MD, 412-692-5427, paul.szabolcs@chp.edu

investigators: Paul Szabolcs, MD,UPMC Children's Hospital Of Pittsburgh

trial center locations: United States

• United States, Pennsylvania
  UPMC Children’s Hospital of Pittsburgh
  Shawna McIntyre, RN, 412-692-5552, mcintyresm@upmc.edu