Clinical trial NCT04528355: 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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Primary Immunodeficiency (PID)
Congenital Bone Marrow Failure Syndromes
Inherited Metabolic Disorders (IMD)
Hereditary Anemias
Inflammatory Conditions
Keywords: 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
Lymphocyte Signaling defects
Congenital Amegakaryocytic Thrombocytopenia (CAMT)
Osteopetrosis
Hurler syndrome (MPS I)
Hurler syndrome (MPS II)
Krabbe Disease, also known as Globoid Cell Leukodystrophy
Metachromatic leukodystrophy (MLD)
X-linked adrenoleukodystrophy (ALD)
Alpha Mannosidosis
Gaucher Disease
Thalassemia major
Sickle cell disease (SCD)
Diamond Blackfan Anemia (DBA)
Crohn's Disease
Inflammatory Bowel Disease
IPEX or IPEX-like Syndromes
Rheumatoid Arthritis
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2020-08-27
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients with Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation

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.

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.

Primary outcomes:
measure: incidence of acute graft versus host disease (GVHD)
timeFrame: up to 5 years
measure: overall survival after HSCT
timeFrame: up to 5 years
Secondary outcomes:
measure: Describe degree of engraftment, based upon chimerism data
timeFrame: up to 5 years
measure: Describe probability to discontinue systemic immunosuppression medications
timeFrame: by 6, 9, and 12 months post-HSCT
measure: Describe the tempo of immune reconstitution
timeFrame: over the first year post transplant
measure: Describe the use of donor leukocyte infusion (DLI)
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: UPMC Children's Hospital of Pittsburgh
name: Paul Szabolcs, MD
role: PRINCIPAL_INVESTIGATOR
References: