Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT

NCT01962415 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY19060337
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the efficacy of using a reduced-intensity condition (RIC) regimen with umbilical cord blood transplant (UCBT), double cord UCBT, matched unrelated donor (MUD) bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) in patients with non-malignant disorders that are amenable to treatment with hematopoietic stem cell transplant (HSCT). After transplant, subjects will be followed for late effects and for ongoing graft success.

Conditions

Congenital Bone Marrow Failure Syndromes; Inherited Metabolic Disorders (IMD); Hereditary Anemias; Inflammatory Conditions; Systemic Juvenile Idiopathic Arthritis (sJIA); Juvenile Rheumatoid Arthritis (JRA); Primary Immunodeficiency (PID)

Keywords

Severe Combined Immune Deficiency (SCID); 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); X-linked Hyper IgM (XHIM) syndrome; IPEX syndrome; Chediak - Higashi Syndrome; Autoimmune Lymphoproliferative Syndrome (ALPS); Hemophagocytic Lymphohistiocytosis (HLH) syndromes; Lymphocyte Signaling defects; Dyskeratosis Congenita (DC); Congenital Amegakaryocytic Thrombocytopenia (CAMT); Osteopetrosis; Mucopolysaccharidoses; Hurler syndrome (MPS I); Hunter syndrome (MPS II); Leukodystrophies; Krabbe Disease; 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; Hematopoietic Stem Cell Transplant (HSCT); Congenital transfusion dependent anemias; Globoid cell leukodystrophy; Hereditary diffuse leukoencephalopathy with spheroids (HDLS); Systemic Juvenile Idiopathic Arthritis (sJIA); Juvenile Rheumatoid Arthritis (JRA)

Outcome Measures

Primary Outcomes (5)

• Post-transplant treatment-related mortality (TRM)

  The number of deaths related to the research intervention at day 100, 6 months, and 1 year post-transplant.

  1 year post-transplant

• Neurodevelopmental milestones

  Evaluation of the pace of attaining neurodevelopmental milestones after reduced-intensity conditioning as compared to myeloablative conditioning historical controls from the target population(s).

  1 year post-transplant

• Immune Reconstitution

  Evaluation of the pace of immune reconstitution.

  1 year post-transplant

• Severe opportunistic infections

  Evaluation of the incidence of severe opportunistic infections.

  1 year post-transplant

• GVHD occurrence

  Description of the incidence of acute graft versus host disease (GVHD) (II-IV) and chronic extensive GVHD.

  1 year post-transplant

Secondary Outcomes (6)

• Donor cell engraftment

  6 months post-transplant

• Normal enzyme level

  1 year post-transplant

• Neutrophil recovery

  1 year post-transplant

• Platelet recovery

  1 year post-transplant

• Grade 3-4 organ toxicity

  1 year post-transplant

Study Arms (2)

UCBT:transfusion dependent anemias or increased rejection risk

EXPERIMENTAL

Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT.

Drug: Hydroxyurea; Drug: Alemtuzumab; Drug: Fludarabine; Drug: Melphalan; Drug: Thiotepa

BMT, PBSCT and not transfusion dependent UCBT

EXPERIMENTAL

Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT.

Drug: Hydroxyurea; Drug: Alemtuzumab; Drug: Fludarabine; Drug: Melphalan; Drug: Thiotepa

Interventions

Hydroxyurea DRUG

Oral administration

Also known as: hydroxycarbamide, Hydrea, Droxia

BMT, PBSCT and not transfusion dependent UCBT; UCBT:transfusion dependent anemias or increased rejection risk

Alemtuzumab DRUG

Intravenous (IV) administration.

Also known as: Campath

BMT, PBSCT and not transfusion dependent UCBT; UCBT:transfusion dependent anemias or increased rejection risk

Fludarabine DRUG

IV administration

Also known as: Fludara

BMT, PBSCT and not transfusion dependent UCBT; UCBT:transfusion dependent anemias or increased rejection risk

Melphalan DRUG

IV administration

Also known as: Melphalan hydrochloride, Alkeran

BMT, PBSCT and not transfusion dependent UCBT; UCBT:transfusion dependent anemias or increased rejection risk

Thiotepa DRUG

IV administration

BMT, PBSCT and not transfusion dependent UCBT; UCBT:transfusion dependent anemias or increased rejection risk

Eligibility Criteria

• Age: 2 Months - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• A 4/6, 5/6 or 6/6 HLA matched related or unrelated UCB unit available that will deliver a pre-cryopreservation total nucleated cell dose of ≥ 3 x 10e7 cells/kg, or double unit grafts, each cord blood unit delivering at least 2 x 10e7 cells/kg OR an 8 of 8 or 7 of 8 HLA allele level matched unrelated donor bone marrow or peripheral blood progenitor graft.
• Adequate organ function as measured by:
• Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥ 50 mL/min/1.73 m2.
• Hepatic transaminases (ALT/AST) ≤ 4 x upper limit of normal (ULN).
• Adequate cardiac function by echocardiogram or radionuclide scan (shortening fraction \> 26% or ejection fraction \> 40% or \> 80% of normal value for age).
• Pulmonary evaluation testing demonstrating CVC or FEV1/FVC of ≥ 50% of predicted for age and/or resting pulse oximeter ≥ 92% on room air or clearance by the pediatric or adult pulmonologist. For adult patients DLCO (corrected for hemoglobin) should be ≥ 50% of predicted if the DLCO can be obtained.
• Written informed consent and/or assent according to FDA guidelines.
• Negative pregnancy test if pubertal and/or menstruating.
• HIV negative.
• A non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to:
• Primary Immunodeficiency syndromes including but not limited to:
• Severe Combined Immune Deficiency (SCID) with NK cell activity
• Omenn Syndrome
• Bare Lymphocyte Syndrome (BLS)
• Combined Immune Deficiency (CID) syndromes

You may not qualify if:

• Allogeneic hematopoietic stem cell transplant within the previous 6 months.
• Any active malignancy or MDS.
• Severe acquired aplastic anemia.
• Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression of clinical symptoms).
• Pregnancy or nursing mother.
• Poorly controlled pulmonary hypertension.
• Any condition that precludes serial follow-up.

Sponsors & Collaborators

• Paul Szabolcs: lead

Study Sites (1)

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Related Publications (2)

• Vander Lugt MT, Chen X, Escolar ML, et al. Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders. Blood Adv. 2020;4(13):3041-3052. Blood Adv. 2020 Aug 11;4(15):3508. doi: 10.1182/bloodadvances.2020002967. No abstract available.

  PMID: 32750127 RESULT

• Vander Lugt MT, Chen X, Escolar ML, Carella BA, Barnum JL, Windreich RM, Hill MJ, Poe M, Marsh RA, Stanczak H, Stenger EO, Szabolcs P. Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders. Blood Adv. 2020 Jul 14;4(13):3041-3052. doi: 10.1182/bloodadvances.2020001940.

  PMID: 32634238 DERIVED

Related Links

• Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders

MeSH Terms

Conditions

Primary Immunodeficiency Diseases; Congenital Bone Marrow Failure Syndromes; Arthritis, Juvenile; Severe Combined Immunodeficiency; Syndrome; Wiskott-Aldrich Syndrome; Leukocyte adhesion deficiency type 1; Granulomatous Disease, Chronic; Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome; Chediak-Higashi Syndrome; Autoimmune Lymphoproliferative Syndrome; Lymphohistiocytosis, Hemophagocytic; Dyskeratosis Congenita; Congenital amegakaryocytic thrombocytopenia; Osteopetrosis; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis II; Sudden Infant Death; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Adrenoleukodystrophy; alpha-Mannosidosis; Gaucher Disease; beta-Thalassemia; Anemia, Sickle Cell; Anemia, Diamond-Blackfan; Crohn Disease; Inflammatory Bowel Diseases; Hereditary Diffuse Leukoencephalopathy with Spheroids

Interventions

Hydroxyurea; Alemtuzumab; fludarabine; fludarabine phosphate; Melphalan; Thiotepa

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Infant, Newborn, Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, X-Linked; Phagocyte Bactericidal Dysfunction; Chronic Disease; Disease Attributes; Albinism; Eye Diseases, Hereditary; Eye Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic; Skin Diseases; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Death, Sudden; Death; Infant Death; Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Leukoencephalopathies; Demyelinating Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Sulfatidosis; Peroxisomal Disorders; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Mannosidase Deficiency Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Red-Cell Aplasia, Pure; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Paul Szabolcs, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Szabolcs, MD

CONTACT

412-692-5427; paul.szabolcs@chp.edu

Shawna McIntyre, RN

CONTACT

412-692-5552; mcintyresm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, BMT-CT at CHP of UPMC and Professor of Pediatrics and Immunology, University of Pittsburgh

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: October 14, 2013
• Study Start: February 4, 2014
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)