Immune Disorder HSCT Protocol

NCT01821781 | Active Not Recruiting Phase 2

• 1 other identifier: 201301135
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study hypothesizes that a reduced intensity immunosuppressive preparative regimen will establish engraftment of donor hematopoietic cells with acceptable early and delayed toxicity in patients with immune function disorders. A regimen that maximizes host immune suppression is expected to reduce graft rejection and optimize donor cell engraftment.

Conditions

Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; IPEX; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

Keywords

Immune deficiency; Immune disorders; Immune dysregulatory; Reduced Intensity; Alemtuzumab; Campath

Outcome Measures

Primary Outcomes (1)

• Number of participants with donor engraftment

  1 year post transplant

Secondary Outcomes (9)

• Major Transplant Related Toxicities

  1 years post transplant

• Time to neutrophil recovery

  within 100 days post transplant

• Number of patient with acute GVHD

  180 days post transplant

• Number of participants with infectious complications

  2 years post transplant

• Time to immune reconstitution

  2 years post transplant

Study Arms (1)

Preparative

EXPERIMENTAL

Drug: Transplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalan

Interventions

Transplant preparative regimen of alemtuzumab, fludarabine, thiotepa, and melphalan DRUG

Between days -23 and -15: alemtuzumab test dose, 3mg IV or SQ Day -14: alemtuzumab, 10mg IV or SQ Day -13: alemtuzumab, 15mg IV or SQ Day -12: alemtuzumab, 20mg IV or SQ Days -8 to -4: fludarabine, 30mg/m2 IV Day -4: thiotepa 4mg/kg IV q 12 hours Day -3: melphalan, 140mg/m2 IV Day 0: stem cell infusion Day +7: G-CSF

Preparative

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \</= 28 years of age
• Performance status \>/= 40
• DLCO \>/= 40%
• LVEF \>/=40% or LVSF \>/=26%
• Serum creatinine \< 2x ULN
• Liver enzymes \</= 5x ULN
• Negative pregnancy test
• Suitably matched donor (6/6 matched sib UCB, 8/8 matched sib BM or PBSC, 5-6/6 matched unrelated UCB, 7-8/8 matched unrelated BM, double cord)

You may not qualify if:

• Known diagnosis of HIV I/II
• Pregnant or breastfeeding
• Uncontrolled invasive fungal or bacterial infections within 1 month prior to starting alemtuzumab
• Uncontrolled viral infection within 1 week prior to starting alemtuzumab

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Bhatt ST, Schulz G, Hente M, Slater A, Murray L, Shenoy S, Bednarski JJ. A single-center experience using alemtuzumab, fludarabine, melphalan, and thiotepa as conditioning for transplantation in pediatric patients with chronic granulomatous disease. Pediatr Blood Cancer. 2020 Jan;67(1):e28030. doi: 10.1002/pbc.28030. Epub 2019 Oct 10.

  PMID: 31599480 DERIVED

MeSH Terms

Conditions

Severe Combined Immunodeficiency; Granulomatous Disease, Chronic; Bruton type agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM Immunodeficiency Syndrome; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immunodeficiency; Lymphohistiocytosis, Hemophagocytic; Autoimmune Lymphoproliferative Syndrome; Lymphoproliferative Disorders; Immunologic Deficiency Syndromes; Immune System Diseases

Interventions

fludarabine; Thiotepa; Melphalan

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Dysgammaglobulinemia; Blood Protein Disorders; 22q11 Deletion Syndrome; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Lymphatic Abnormalities; Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Albinism; Eye Diseases, Hereditary; Eye Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Autoimmune Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2013
• First Posted: April 1, 2013
• Study Start: April 29, 2013
• Primary Completion: April 25, 2025
• Study Completion: April 1, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (1)