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

Primary Immunodeficiency (PID) Clinical Trial

— PRO-RIC  

Official 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04528355
• Other study ID #: STUDY20070105
• Status: Recruiting
• Start date: August 20, 2020
• Est. completion date: June 30, 2026

Study information

• Verified date: February 2024
• Source: University of Pittsburgh
• Contact: Paul Szabolcs, MD
• Phone: 412-692-5427
• Email: paul.szabolcs[@]chp.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bone Marrow Failure Disorders
• Congenital Bone Marrow Failure Syndromes
• Hereditary Anemias
• Inflammatory Conditions
• Inherited Metabolic Disorders (IMD)
• Metabolic Diseases
• Pancytopenia
• Primary Immunodeficiency (PID)
• Primary Immunodeficiency Diseases
• Syndrome

Intervention

Drug:
• data collection
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.

Locations

Country	Name	City	State
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Paul Szabolcs

Country where clinical trial is conducted

United States, 

Outcome

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