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

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ClinicalTrials.gov Identifier: NCT04528355
Recruitment Status : Recruiting
First Posted : August 27, 2020
Last Update Posted : February 13, 2023
Sponsor:
Information provided by (Responsible Party):
Paul Szabolcs, University of Pittsburgh

Tracking Information
First Submitted Date August 18, 2020
First Posted Date August 27, 2020
Last Update Posted Date February 13, 2023
Actual Study Start Date August 20, 2020
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 6, 2020)
  • incidence of acute graft versus host disease (GVHD) [ Time Frame: up to 5 years ]
    grades 3-4, chronic extensive GVHD
  • overall survival after HSCT [ Time Frame: up to 5 years ]
    review of the existing medical records to check on the participant's survival status
Original Primary Outcome Measures
 (submitted: August 25, 2020)
  • incidence of acute graft versus host disease (GVHD) [ Time Frame: up to 5 years ]
    grades 3-4, chronic extensive GVHD
  • overall survival after HSCT [ Time Frame: up to 5 years ]
Change History
Current Secondary Outcome Measures
 (submitted: October 6, 2020)
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures
 (submitted: August 25, 2020)
  • Describe degree of engraftment, based upon chimerism data [ Time Frame: up to 5 years ]
  • Describe probability to discontinue systemic immunosuppression medications [ Time Frame: by 6, 9, and 12 months post-HSCT ]
  • Describe the tempo of immune reconstitution [ Time Frame: over the first year post transplant ]
  • Describe the use of donor leukocyte infusion (DLI) [ Time Frame: up to 5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With 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)
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.
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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population patients with Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation
Condition
  • Primary Immunodeficiency (PID)
  • Congenital Bone Marrow Failure Syndromes
  • Inherited Metabolic Disorders (IMD)
  • Hereditary Anemias
  • Inflammatory Conditions
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.
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: August 25, 2020)		 50
Original Estimated Enrollment Same as current
Estimated Study Completion Date June 30, 2026
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 2 Months to 60 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Paul Szabolcs, MD 412-692-5427 paul.szabolcs@chp.edu
Contact: Shawna McIntyre, RN 412-692-5552 mcintyresm@upmc.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04528355
Other Study ID Numbers STUDY20070105
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement
Plan to Share IPD: No
Current Responsible Party Paul Szabolcs, University of Pittsburgh
Original Responsible Party Same as current
Current Study Sponsor Paul Szabolcs
Original Study Sponsor Same as current
Collaborators Not Provided
Investigators
Principal Investigator: Paul Szabolcs, MD UPMC Children's Hospital of Pittsburgh
PRS Account University of Pittsburgh
Verification Date February 2023