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

Sponsor

Paul Szabolcs (Other)

Overall Status

Recruiting

CT.gov ID

NCT04528355

Collaborator

(none)

Enrollment

Location

70.3

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Primary Immunodeficiency (PID) Congenital Bone Marrow Failure Syndromes Inherited Metabolic Disorders (IMD) Hereditary Anemias Inflammatory Conditions	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 Design

Study Type:

Observational

Anticipated Enrollment :

50 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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)

Actual Study Start Date :

Aug 20, 2020

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Jun 30, 2026

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Describe degree of engraftment, based upon chimerism data [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
Describe probability to discontinue systemic immunosuppression medications [by 6, 9, and 12 months post-HSCT]
review of the existing medical records to check on the participant's current medications
Describe the tempo of immune reconstitution [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
Describe the use of donor leukocyte infusion (DLI) [up to 5 years]
review of the existing medical records to check on the participant's need for DLI

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Months to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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

Congenital Bone Marrow Failure Syndromes

Congenital Amegakaryocytic Thrombocytopenia (CAMT)
Osteopetrosis

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

Hereditary Anemias

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224

Sponsors and Collaborators

Paul Szabolcs

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Paul Szabolcs, Chief, BMT-CT at CHP of UPMC and Professor of Pediatrics and Immunology, University of Pittsburgh, University of Pittsburgh

ClinicalTrials.gov Identifier:

NCT04528355

Other Study ID Numbers:

STUDY20070105

First Posted:

Aug 27, 2020

Last Update Posted:

Feb 11, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Paul Szabolcs, Chief, BMT-CT at CHP of UPMC and Professor of Pediatrics and Immunology, University of Pittsburgh, University of Pittsburgh

Severe Combined Immune Deficiency (SCID) with NK cell activity

Omenn Syndrome

Bare Lymphocyte Syndrome (BLS)

Combined Immune Deficiency (CID) syndromes

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