Bone Marrow Transplant With Abatacept for Non-Malignant Diseases

NCT01917708 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB00069836
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, phase I study to assess the tolerability of abatacept when combined with cyclosporine and mycophenolate mofetil as graft versus host disease prophylaxis in children undergoing unrelated hematopoietic stem cell transplant for serious non-malignant diseases as well as to assess the immunological effects of abatacept. Participants will be followed for 2 years.

Conditions

Hurler Syndrome; Fanconi Anemia; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Shwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia; Thalassemia Major; Hemophagocytic Lymphohistiocytosis; Sickle Cell Disease

Keywords

non malignant conditions; blood and marrow transplant

Outcome Measures

Primary Outcomes (1)

• Tolerability of Abatacept

  The primary endpoint for this trial will be tolerability, defined in terms of the success in administering all prescribed doses of abatacept. Abatacept will be deemed to be poorly tolerated if any of the following conditions are met: * More than one dose is withheld. * Death from an infection that occurs within 30 days of receiving the last prescribed dose of abatacept, but that is not preceded by systemic immunosuppressive therapy for GVHD * Post-transplant lymphoproliferative disorder (PTLD) that occurs within 100 days of receiving the last prescribed dose, but that is not preceded by systemic immunosuppressive therapy for GVHD. If less than 4 patients (of at least 18 evaluable patients) tolerate abatacept poorly, abatacept will be deemed tolerable. If there are fewer than 18 evaluable patients, if 3 of the first 10 patients treated tolerate abatacept poorly, abatacept will be deemed tolerable.

  1 year post-transplant

Secondary Outcomes (17)

• Proportion of Participants Experiencing Regimen-related Toxicity (RRT)

  Day 42 post-transplant

• Days until Neutrophil Recovery

  1 year post-transplant

• Days until Platelet Recovery

  1 year post-transplant

• Number of Participants with Non-engraftment

  1 year post-transplant

• Number of Participants with Secondary Graft Failure

  1 year post-transplant

Study Arms (1)

Abatacept

EXPERIMENTAL

4 doses of abatacept 10 mg/kg/dose will be given on days -1, +5, +14, and +28.

Drug: Abatacept

Interventions

Abatacept DRUG

All patients will receive 4 doses of abatacept in addition to standard GVHD prophylaxis with cyclosporine and mycophenolate mofetil.

Also known as: Orencia

Abatacept

Eligibility Criteria

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

You may qualify if:

• Must be between the ages of 0-21 years at the time of admission for transplant.
• Must have one of the following diseases:
• Glanzmann thrombasthenia
• Wiskott-Aldrich syndrome or other combined immune deficiency
• Chronic-granulomatous disease
• Severe congenital neutropenia (with resistance to granulocyte-colony stimulating factor (GCSF) or chronic requirement of GCSF doses ≥10 mcg/kg)
• Leukocyte adhesion deficiency
• Shwachman-Diamond syndrome
• Diamond-Blackfan anemia ((transfusion dependent, including steroid failure or inability to wean steroids)
• Thalassemia major
• Fanconi anemia
• Hemophagocytic lymphohistiocytosis (inherited or acquired refractory to therapy or with recurrent episodes of hyperinflammation)
• Dyskeratosis-congenita
• Hurler Syndrome
• Chediak-Higashi syndrome

You may not qualify if:

• Human leukocyte antigen (HLA) matched related donor.
• Severe combined immune deficiency.
• Bridging (portal to portal) fibrosis or cirrhosis of the liver.
• Severe renal dysfunction defined as estimated glomerular filtration rate (GFR) of \<60 ml/min/1.73m2.
• Severe cardiac dysfunction defined as shortening fraction \< 25%.
• Neurologic impairment other than hemiplegia, defined as full-scale intelligence quotient (IQ) less than or equal to 70, quadriplegia or paraplegia, inability to ambulate, or any impairment resulting in decline of Lansky performance score to \< 70%.
• Clinical stroke within 6 months of anticipated transplant.
• Karnofsky or Lansky functional performance score \< 50%
• HIV infection.
• Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
• Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
• Patient or patient's guardian(s) unable to understand the nature and risks inherent in the blood and marrow transplant process.
• History of non-compliance severe enough in the estimation of the treating team to preclude the patient from undergoing unrelated donor transplantation.
• Patient is pregnant or lactating
• Patients HLA antibody testing demonstrates an antibody directed against a disparate HLA molecule.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I; Fanconi Anemia; Thrombasthenia; Wiskott-Aldrich Syndrome; Granulomatous Disease, Chronic; Neutropenia, Severe Congenital, Autosomal Recessive 3; Leukocyte adhesion deficiency type 1; Shwachman-Diamond Syndrome; Anemia, Diamond-Blackfan; Dyskeratosis Congenita; Chediak-Higashi Syndrome; Anemia, Aplastic; beta-Thalassemia; Lymphohistiocytosis, Hemophagocytic; Anemia, Sickle Cell

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Anemia, Hypoplastic, Congenital; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; DNA Repair-Deficiency Disorders; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Lymphopenia; Leukopenia; Cytopenia; Leukocyte Disorders; Genetic Diseases, X-Linked; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Phagocyte Bactericidal Dysfunction; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Exocrine Pancreatic Insufficiency; Pancreatic Diseases; Digestive System Diseases; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Lipomatosis; Red-Cell Aplasia, Pure; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic; Skin Diseases; Albinism; Eye Diseases, Hereditary; Eye Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• John T Horan, MD

  Children's Healthcare of Atlanta/Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 24, 2013
• First Posted: August 7, 2013
• Study Start: January 1, 2014
• Primary Completion: September 19, 2019
• Study Completion: September 19, 2019
• Last Updated: December 26, 2019

Record last verified: 2019-12

Locations

US (1)