CompletedNCT01917708Updated Dec 26, 2019

Bone Marrow Transplant With Abatacept for Non-Malignant Diseases

A Phase 1 interventional study of Abatacept in Hurler Syndrome, Fanconi Anemia and Glanzmann Thrombasthenia, sponsored by Emory University. Completed at 1 site in United States. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2019-12-26.

Sponsored by Emory University · Phase 1, Interventional, and Supportive care

From the registry’s dates

Primary completion was Sep 2019, 7 years ago, and no results have been posted to the registry.

Phase: Phase 1
Study type: Interventional
Enrollment: 10
Allocation: Not applicable
Ages: Up to 21 Years
Sex: All

Study 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.

Read the 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 reduced intensity conditioning for children with non-malignant diseases (NMD). This study will have the following Specific Aims:

Specific Aim #1: To conduct a multicenter pilot assessing the tolerability of abatacept (n=10). Patients will receive four doses (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. Abatacept will be combined with cyclosporine and mycophenolate mofetil.

Specific Aim #2: To examine the immunological effects of abatacept in this setting.

Three reduced intensity conditioning regimens that have been shown to be effective in achieving sustained engraftment in patients with non-malignant diseases are available for use, depending on the patient's disease:

Patients with Fanconi anemia will receive fludarabine, low dose cyclophosphamide, and anti-thymocyte globulin.
Patients with severe aplastic anemia will receive low dose total body irradiation, fludarabine, cyclophosphamide, and anti-thymocyte globulin.
Patients with other NMD will receive either the low dose total body irradiation regimen or an alemtuzumab, fludarabine, thiotepa, and melphalan regimen.

Conditions studied

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

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Keywords

non malignant conditions
blood and marrow transplant

In context

Anemia

1,733 studies on the registry are indexed under Anemia; 246 are open to participants now.

This study's enrollment of 10 is below the median of 94 across 1,291 interventional studies indexed under Anemia.

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Lead sponsor

Emory University is the lead sponsor of 1,386 studies on the registry; 236 are open to participants now.

Of its 229 completed or terminated interventional studies of FDA-regulated products, 174 (76%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: Up to 21 Years
Sexes eligible: All
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 (with resistance to granulocyte-colony stimulating factor (GCSF) or chronic requirement of GCSF doses ≥10 mcg/kg)
5. Leukocyte adhesion deficiency
6. Shwachman-Diamond syndrome
7. Diamond-Blackfan anemia ((transfusion dependent, including steroid failure or inability to wean steroids)
8. Thalassemia major
9. Fanconi anemia
10. Hemophagocytic lymphohistiocytosis (inherited or acquired refractory to therapy or with recurrent episodes of hyperinflammation)
11. Dyskeratosis-congenita
12. Hurler Syndrome
13. Chediak-Higashi syndrome
14. Acquired (immune; non-inherited, non-congenital) severe aplastic anemia
15. Sickle cell disease (SCD) (Hgb SS or S-Beta 0 thalassemia) will be eligible between ages 3 and 9.99 and with severe disease.
16. Other inherited or congenital marrow failure syndromes complicated by severe aplastic anemia
17. Other inherited or congenital red blood cell disorders requiring monthly chronic transfusion therapy.
18. Congenital platelet disorders requiring frequent platelet transfusions (patient must have received at least 10 transfusions in the last 3 years).
19. 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 at least a 7/8 match (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 total nucleated cell (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

Exclusion Criteria:

Human leukocyte antigen (HLA) matched related donor.
Severe combined immune deficiency.
Bridging (portal to portal) fibrosis or cirrhosis of the liver.
Pulmonary: diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin), forced expiratory volume (FEV1) or forced vital capacity (FVC) \< 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 (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.

Study design

Phase: Phase 1
Primary purpose: Supportive care
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 10 participants (actual)

Study arms

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

Interventions

DrugAbatacept
All patients will receive 4 doses of abatacept in addition to standard GVHD prophylaxis with cyclosporine and mycophenolate mofetil.
Also known as: Orencia

What researchers measure

Primary outcomes

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.
Time frame: 1 year post-transplant

Secondary outcomes

Proportion of Participants Experiencing Regimen-related Toxicity (RRT)
Regimen-related toxicity is scored according to the Bearman scale. Major RRT, defined as grade 4 (causing death) in any organ system or grade 3 for pulmonary, cardiac, renal, oral mucosal, neurologic or hepatic, will be recorded.
Time frame: Day 42 post-transplant
Days until Neutrophil Recovery
Neutrophil recovery is defined as the first of 3 consecutive days following the nadir that the absolute neutrophil count is at least 500/µl.
Time frame: 1 year post-transplant
Days until Platelet Recovery
Platelet recovery is defined as the first day that the platelet count is at least 20 thousand/µl without a transfusion in the preceding 7 days.
Time frame: 1 year post-transplant
Number of Participants with Non-engraftment
Non-engraftment is defined as lack of neutrophil recovery (defined as absolute neutrophil count (ANC )\>0.5 \*109/L for three consecutive days) by 28 days post-transplant or neutrophil recovery with lack of myeloid donor chimerism.
Time frame: 1 year post-transplant
Number of Participants with Secondary Graft Failure
Secondary graft failure is defined by initial engraftment but subsequent development of an ANC \<0.5\*109/L for fourteen consecutive days.
Time frame: 1 year post-transplant
Number of Participants with Graft Loss
Graft loss is defined by initial engraftment (assessed by neutrophil recovery and donor chimerism) with the subsequent loss of donor myeloid chimerism (regardless whether persistent neutropenia develops).
Time frame: 1 year post-transplant
Number of Participants Experiencing Cytomegalovirus (CMV) Viremia
Cytomegalovirus (CMV) viremia is defined as positive blood antigen or polymerase chain reaction (PCR) test.
Time frame: Up to Day 180
Number of Participants Experiencing CMV Invasive Disease
CMV invasive disease is defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures.
Time frame: 1 year post-transplant
Number of Participants Experiencing Post-transplant Lymphoproliferative Disorder (PTLD)
Post-transplant lymphoproliferative disorder (PTLD) is defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures and the World Health Organization's Classification of Tumours of Haematopoietic and Lymphoid Tissues.
Time frame: 1 year post-transplant
Number of Participants Experiencing Other Infections
Infections other than CMV viremia, CMV invasive disease, and PTLD is defined in accordance with the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures.
Time frame: 1 year post-transplant
Number of Participants Experiencing Immune Reconstitution
Immune reconstitution is assessed by the day 100 cluster of differentiation 4 (CD4+) T cell count and by the reaccumulation of natural killer (NK) cells, B cells, total T cells, and cluster of differentiation 8 (CD8+) T cells as assessed by multicolor flow cytometry.
Time frame: 1 year post-transplant
Number of Participants Experiencing Acute Graft Versus Host Disease (GVHD)
Early onset (before day 100) and late onset (after day 100) acute GVHD is assessed according to the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures using the NIH consensus criteria.
Time frame: Up to 1 year post-transplant
Number of Participants Experiencing Chronic GVHD
Chronic GVHD, including overlap syndrome, is assessed according to the Blood and Marrow Transplant Clinical Trials Network Manual of Procedures using the NIH consensus criteria.
Time frame: 2 years post-transplant
Immune Suppression-Free Survival Rate
Participant survival while off of immunosuppressive agents.
Time frame: 1 year post-transplant
Immune Suppression-Free and Disease-Free Survival Rate
Participant disease-free survival while off of immunosuppressive agents.
Time frame: 1 year post-transplant
Disease-free Survival Rate
Disease-free survival is defined as survival without recurrence of underlying disease.
Time frame: 1 year post-transplant
Overall Survival Rate
Overall-survival is defined as survival with or without relapse of underlying disease
Time frame: 1 year post-transplant

Study locations

1 site

Children's Healthcare of Atlanta
Atlanta, Georgia 30322, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 26, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01917708
Lead sponsor: Emory University
Responsible party: John Horan (Associate Professor, Emory University) — Principal investigator
First posted: Aug 7, 2013
Start date: Jan 2014
Primary completion: Sep 19, 2019
Completion: Sep 19, 2019
Last update: Dec 26, 2019

Study contacts

John T Horan, MD

principal investigator · Children's Healthcare of Atlanta/Emory University

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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