Acute GVHD Suppression Using Costimulation Blockade to Expand Non-malignant Transplant

Running, not enrolling · Phase 2

Conditions studied: Graft Versus Host Disease

In brief

This trial will see if extended abatacept administration (combined with a standard regimen of tacrolimus and mycophenolate mofetil) will prevent acute and chronic graft-versus-host disease (GVHD) in children and adolescents receiving unrelated donor (URD) hematopoietic stem cell transplantation (HSCT), without compromising their engraftment or reconstitution of protective immunity to infection. The study will enroll 30 pediatric patients with serious non-malignant hematologic diseases (NMHD) undergoing URD HSCT. The trial will include patients with 7/8 donors and those with 8/8 (matched) donors. All participants will receive 8 doses of abatacept. Recruitment is expected to last for about 2 years and participants will be followed for up to 3 years.

Key facts

Study ID

NCT03924401

Run by

Emory University

People needed

30

Starts

2019-08-22

Expected to finish

2027-03-01

Last updated by the study team

2026-02-25

Who can join

Age: any, up to 20. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients with sickle cell disease (stratum 1) must be between the ages of 3-20.99 years and patients with other diseases (stratum 2) between the ages of 0-20.99 years at the time of admission for transplant.
• Must have one of the following diseases:
• Glanzmann thrombasthenia
• 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 (DBA; transfusion dependent, including steroid failure or inability to wean steroids)
• Thalassemia major
• FA
• Dyskeratosis congenita
• Chediak Higashi syndrome
• Acquired (immune; non-inherited, non-congenital) SAA
• Any genotypic form of SCD with severe disease, defined as one or more of the following criteria:
• Previous clinical stroke, as evidenced by a neurological deficit lasting longer than 24 hours, which is accompanied by radiographic evidence of ischemic brain injury and cerebral vasculopathy.
• Asymptomatic cerebrovascular disease, as evidenced by one the following:
• Progressive silent cerebral infarction, as evidenced by serial MRI scans that demonstrate the development of a succession of lesions (at least two temporally discreet lesions, each measuring at least 3 mm in greatest dimension on the most recent scan) or the enlargement of a single lesion, initially measuring at least 3 mm. Lesions must be visible on T2-weighted MRI sequences.
• Cerebral arteriopathy, as evidenced by abnormal TCD testing (confirmed elevated velocities in any single vessel of time-averaged mean of the maximum velocity (TAMMV) > 200 cm/sec for non-imaging TCD) or by significant vasculopathy on magnetic resonance angiograph (MRA; greater than 50% stenosis of > 2 arterial segments or complete occlusion of any single arterial segment).
• Frequent (3 or more per year for preceding 2 years) painful vaso-occlusive episodes (defined as episode lasting 4 hours or more and requiring hospitalization or outpatient treatment with parenteral opioids). If patient is on hydroxyurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 2 years prior to the start of this drug.
• Recurrent (3 or more in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy.
• Any combination of 3 or more acute chest syndrome episodes and vaso-occlusive pain episodes (defined as above) yearly for 3 years. If patient is on hydroxurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 3 years prior to the start of this drug.
• Other inherited or congenital marrow failure syndromes complicated by SAA
• Other inherited or congenital red blood cell disorders requiring monthly chronic transfusion therapy.
• Congenital platelet disorders requiring frequent platelet transfusions (patient must have received at least 10 transfusions in the last 3 years).
• Other inherited or congenital granulocyte disorders resulting in at least three inpatient hospitalizations in the past three years for infection.

You may not qualify if…

• HLA matched related donor
• Pulmonary dysfunction defined as diffusing capacity of the lungs for carbon monoxide (DLCO; corrected for hemoglobin), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) < 40% of predicted. In a child unable to perform pulmonary function testing, a chronic need for supplemental oxygen will serve as the exclusionary criterion.
• Renal dysfunction defined as estimated glomerular filtration rate (GFR) of <60 ml/min/1.73m2.
• Severe cardiac dysfunction defined as shortening fraction < 25%.
• Bridging (portal to portal) fibrosis or cirrhosis of the liver
• 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 HSCT.
• Patient or patient's guardian(s) unable to understand the nature and risks inherent in the HSCT 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.
• Patient with a 7/8 URD donor and HLA antibody testing (see below) demonstrating an antibody directed against a donor disparate HLA molecule.

Where it is running

• Children's of Alabama — Birmingham, Alabama, United States
• Nemours/Alfred I. DuPont Hospital for Children — Wilmington, Delaware, United States
• Childrens Healthcare of Atlanta — Atlanta, Georgia, United States
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• University of Mississippi Medical Center, Children's Center for Cancer and Blood Disorders — Jackson, Mississippi, United States
• Hackensack Meridian Health — Hackensack, New Jersey, United States
• Oishei Children's Hospital — Buffalo, New York, United States
• Columbia University Irving Medical Center — New York, New York, United States

Full record on ClinicalTrials.gov

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