Abatacept Reduced Intensity for Non-Malignant Diseases (Aba NMD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Emory University
Information provided by (Responsible Party):
Elizabeth Stenger, Emory University
ClinicalTrials.gov Identifier:
First received: July 24, 2013
Last updated: April 11, 2016
Last verified: April 2016
This is a randomized, open-label multicenter pilot study comparing two dose numbers of abatacept. The study is assessing the tolerability of 4 and 6 doses 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.

Condition Intervention Phase
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
Hemophagocytic Lymphohistiocytosis
Drug: 4 doses of abatacept
Drug: 6 doses of abatacept
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Abatacept for Post-Transplant Immune Suppression in Children and Adolescents Receiving Allogeneic Hematopoietic Stem Cell Transplants for Non-Malignant Disease: a Dose Assessment Pilot

Resource links provided by NLM:

Further study details as provided by Emory University:

Primary Outcome Measures:
  • Tolerability of abatacept [ Time Frame: 2 years after enrollment ] [ Designated as safety issue: Yes ]
    To assess the tolerability of four and six doses 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.

Secondary Outcome Measures:
  • Immunological effects [ Time Frame: 2 years after enrollment ] [ Designated as safety issue: No ]
    To compare the immunological effects of the two dose levels.

Estimated Enrollment: 20
Study Start Date: January 2014
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 4 dose
4 doses of abatacept received on days -1, +5, +14 and +28.
Drug: 4 doses of abatacept
4 doses of abatacept received on days -1, +5, +14 and +28.
Active Comparator: 6 dose
6 doses of abatacept received on days -1, +5, +14, +28, +56, and +84.
Drug: 6 doses of abatacept
6 doses of abatacept received on days -1, +5, +14, +28, +56, and +84.

Detailed Description:

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only viable cure for children who suffer from a wide variety of rare, serious non-malignant diseases, such as Fanconi Anemia, Hurler syndrome, and hemophagocytic lymphohistiocytosis. A major obstacle to the success of HSCT is morbidity and mortality from graft versus host disease (GVHD), driven by donor T cells recognizing and reacting against disparate host antigens. This trial is being conducted as a step toward testing the long-term hypothesis that the costimulation blockade agent abatacept can be added to a standard post-transplant GVHD prophylaxis regimen, cyclosporine and mycophenolate mofetil, to improve disease-free survival after unrelated hematopoietic stem cell transplantation (HSCT) using low dose total body irradiation based conditioning for children with non-malignant diseases. This study will have the following Specific Aims.

Specific Aim #1: To conduct a randomized, open-label multicenter pilot, assessing the tolerability of two dose numbers of abatacept (n=20). Patients will be randomly assigned to receive four doses (arm A;10 mg/kg IV on days -1, +5, +14 and +28), a schedule well tolerated by adolescents and adults with hematologic malignancies in a previous pilot, or six doses (arm B;10 mg/kg IV on days -1, +5, +14, +28, +56 and +84). Abatacept will be combined with cyclosporine and mycophenolate mofetil.

Specific Aim #2: to compare the immunological effects of four and six doses.


Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Must be between the ages of 0-21 years at the time of admission for transplant.
  • Must have one of the following diseases:

    1. Glanzmann thrombasthenia
    2. Wiskott-Aldrich syndrome or other combined immune deficiency
    3. Chronic-granulomatous disease
    4. Severe congenital neutropenia
    5. Leukocyte adhesion deficiency
    6. Shwachman-Diamond syndrome
    7. Diamond-Blackfan anemia (transfusion dependent)
    8. Thalassemia major
    9. Fanconi anemia
    10. Hemophagocytic lymphohistiocytosis
    11. Dyskeratosis-congenita
    12. Hurler Syndrome
    13. Chediak-Higashi syndrome
    14. Acquired (immune; non-inherited, non-congenital) severe aplastic anemia
    15. Other inherited or congenital marrow failure syndromes complicated by severe aplastic anemia
    16. Other inherited or congenital red blood cell disorders requiring monthly chronic transfusion therapy.
    17. Congenital platelet disorders requiring frequent platelet transfusions (patient must have received at least 10 transfusions in the last 3 years).
    18. Other inherited or congenital granulocyte disorders resulting in at least three inpatient hospitalizations in the past three years for infection.
  • Must have an unrelated adult donor (marrow or PBSC) who is matched at least seven of eight HLA alleles (A, B, C, DRB1; the mismatch can be at an allele or antigen level)* or an unrelated cord blood unit that is matched at least seven of eight loci (A, B and C antigen level-DRB1 allele level) and provides a minimum pre-cryopreservation TNC dose of 7.5 x 107 TNC/kg recipient weight. Mismatches at the DRB1 locus may be at an antigen or allele level.

Exclusion Criteria:

  • Human leukocyte antigen (HLA) matched related donor
  • Severe combined immune deficiency.
  • Sickle cell disease.
  • Biopsy proven cirrhosis.
  • Pulmonary: Diffusing capacity of lung for carbon monoxide (corrected for hemoglobin), forced expiratory volume at one second or forced vital capacity < 40% of predicted. In child unable to perform pulmonary function testing, a chronic need for supplemental oxygen will serve as the exclusionary criterion.
  • Severe renal dysfunction defined as estimated glomerular filtration rate of <30 ml/min.
  • Severe cardiac dysfunction defined as shortening fraction < 25%.
  • 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 lack of compliance with medical care that would jeopardize transplant course.
  • Patient is pregnant or lactating
  • Patients HLA antibody testing (see below) demonstrates an antibody directed against a disparate HLA molecule.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01917708

Contact: Jaclyn Smith, MBA 404-785-0692 jaclyn.smith@choa.org

United States, Georgia
Children's Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jaclyn Smith, MBA    404-785-0692    jaclyn.smith@choa.org   
Principal Investigator: Elizabeth Stenger, MD         
Sponsors and Collaborators
Emory University
Principal Investigator: Elizabeth Stenger, MD Children's Healthcare of Atlanta/Emory University
  More Information

Responsible Party: Elizabeth Stenger, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT01917708     History of Changes
Other Study ID Numbers: IRB00069836  AbaReduced Intensity NMD 
Study First Received: July 24, 2013
Last Updated: April 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
non malignant conditions
blood and marrow transplant

Additional relevant MeSH terms:
Anemia, Aplastic
Fanconi Anemia
Anemia, Diamond-Blackfan
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia, Hypoplastic, Congenital
Fanconi Syndrome
Granulomatous Disease, Chronic
Wiskott-Aldrich Syndrome
Lymphohistiocytosis, Hemophagocytic
Mucopolysaccharidosis I
Chediak-Higashi Syndrome
Dyskeratosis Congenita
Bone Marrow Diseases
Exocrine Pancreatic Insufficiency
Pathologic Processes
Hematologic Diseases
Leukocyte Disorders
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders

ClinicalTrials.gov processed this record on July 26, 2016