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

About the study

The ASCENT Trial is a single arm, multi-center, phase II study. The primary objective is to
determine the rejection-free, severe graft-versus-host disease (GVHD)-free survival in
pediatric patients with serious non-malignant hematologic diseases (NMHD) undergoing
unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) with abatacept added to
conventional GVHD prophylaxis. The secondary objective is to characterize the impact of
abatacept on infection and the reconstitution of protective immunity to infection.
Transplanted patients will be followed for 3 years. Weight-based peripheral blood samples
will be drawn longitudinally through two years to evaluate immune reconstitution.

The study will enroll 28 pediatric patients with serious NMHD undergoing URD HSCT. The trial
will include two strata, based on donor matching. Stratum 1 (n=14) will be for patients with
7/8 donors and stratum 2 (n=14) will be for those with 8/8 (matched) donors. All participants
will receive 8 doses of abatacept (10 mg/kg intravenously on days -1, +5, +14, +28, +56, +84,
+112, and +150). Recruitment is expected to last for about 2 years and participants will be
followed for up to 3 years.

This trial will test the hypothesis that extended abatacept administration (combined with a
standard regimen of tacrolimus and mycophenolate mofetil) will effectively prevent acute and
chronic GVHD in children and adolescents receiving URD HSCT, without compromising their
engraftment or reconstitution of protective immunity to infection.

Study point of contact

Elizabeth Stenger, MD, MSc
Ben Watkins, MD


7 United States sites


< 20 Years


Phase 2

Study type








participation requirements

– 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.

– Must have an unrelated adult donor (marrow or PBSC) who is a 7 or 8/8 match

– All patients and/or their parents or legal guardians must sign a written informed
consent. Assent, when appropriate, will be obtained according to institutional

– Must have been evaluated and adequately counseled regarding treatment options by a
pediatric hematologist.

– Negative serum pregnancy test for females of childbearing potential only. Pregnancy
must be excluded before the start of treatment with study drugs and prevented
thereafter by reliable contraceptive methods.

participation restrictions

– 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.


  • Birmingham, Alabama, United States, Children's of Alabama, 35233 [Recruiting]
  • Wilmington, Delaware, United States, Nemours/Alfred I. DuPont Hospital for Children, 19803 [Recruiting]
  • Atlanta, Georgia, United States, Childrens Healthcare of Atlanta, 30322 [Recruiting]
  • Chicago, Illinois, United States, Ann & Robert H. Lurie Children's Hospital of Chicago, 60611 [Recruiting]
  • Boston, Massachusetts, United States, Dana-Farber Cancer Institute, 02215 [Recruiting]
  • Hackensack, New Jersey, United States, Hackensack Meridian Health, 07601 [Recruiting]
  • Buffalo, New York, United States, Oishei Children's Hospital, 14203 [Recruiting]
Last updated 2021-08-05