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

NCT03924401 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB00108549
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Graft Versus Host Disease

Keywords

Pediatrics; Non-malignant hematologic diseases; Severe aplastic anemia; Fanconi anemia; Sickle cell disease; Hematopoietic stem cell transplantation; Thalassemia; Mismatched unrelated donor; Matched unrelated donor

Outcome Measures

Primary Outcomes (1)

• Event-free survival

  Event-free survival is a composite endpoint defined as rejection-free, severe GVHD-free survival. Events for this outcome include death, severe (grade II-IV) acute GVHD up to day 100, moderate to severe chronic GVHD up to 1 year, and/or graft rejection up to 1 year.

  Up to 3 years

Secondary Outcomes (15)

• Cytomegalovirus (CMV) Viremia

  Up to Day 180

• CMV Invasive Disease

  Up to 2 years

• Post-transplant lymphoproliferative disease (PTLD)

  Up to 2 years

• Regimen-Related Toxicity

  Day 42 Post-transplant

• Neutrophil Recovery

  Up to Day 60

Study Arms (1)

Participants Receiving Abatacept

EXPERIMENTAL

Pediatric participants who are undergoing URD HSCT for serious NMHD will receive 8 doses of abatacept in addition to conventional GVHD prophylaxis.

Drug: Abatacept

Interventions

Abatacept DRUG

All patients will receive 8 doses of abatacept (10 mg/kg intravenously on days -1, +5, +14, +28, +56, +84, +112, and +150) in addition to conventional GVHD prophylaxis.

Also known as: Orencia

Participants Receiving Abatacept

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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
• 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:

You may not qualify if:

• HLA matched related donor
• 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.

Sponsors & Collaborators

• Emory University: lead
• Thrasher Research Fund: collaborator
• Sickle Cell Transplant Advocacy & Research Alliance (STAR): collaborator
• Aflac Cancer and Blood Disorders Center: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (9)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Nemours/Alfred I. DuPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Childrens Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Mississippi Medical Center, Children's Center for Cancer and Blood Disorders

Jackson, Mississippi, 39216, United States

Location

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

Location

Oishei Children's Hospital

Buffalo, New York, 14203, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease; Anemia, Aplastic; Fanconi Anemia; Anemia, Sickle Cell; Thalassemia

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Immune System Diseases; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Anemia, Hypoplastic, Congenital; Congenital Bone Marrow Failure Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies

Intervention Hierarchy (Ancestors)

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

Study Officials

• John Horan, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: The trial will include two strata: one for patients with a 7/8 matched donor and one for those with a matched 8/8 donor.

Study Record Dates

• First Submitted: April 19, 2019
• First Posted: April 23, 2019
• Study Start: August 22, 2019
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)