A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency
A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency
Background:
People with GATA-binding factor 2 (GATA2) deficiency have a mutation on the GATA2 gene. This gene affects immune function. People with this disease are prone to serious infections; in time, they may develop blood cancers. A hematopoietic stem cell (HSC) transplant can cure GATA2 deficiency, but using stem cells donated by other people can cause serious side effects.
Objective:
To test a new drug (Briquilimab) to see if it can make HSC transplants safer.
Eligibility:
People aged 6 to 70 years who have GATA2 deficiency.
Design:
Participants will be screened. They will have a physical exam, with blood and urine tests. They will have tests of their heart and lung function. They may have a bone marrow biopsy: Their hip will be numbed; a large needle will be inserted to draw out tissue from inside the pelvis.
Participants will have a central venous catheter placed in a vein of the neck or chest. This will be used to draw blood and administer drugs.
Briquilimab will be given through the catheter about 11 days before the transplant. This is part of conditioning: preparing the body to receive the new stem cells. Conditioning also includes other medications and total body irradiation.
Donor stem cells will be administered through the catheter. Participants will receive other approved drugs to help prevent side effects.
Participants will stay in the hospital from the beginning of the conditioning until several weeks after the transplant. They will remain in the local area for 100 days after discharge; they will come to the clinic at least once a week during this time. Follow-up visits will continue for 3 years....
Background:
Primary Objective:
-To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant in participants with GATA2 deficiency
Eligibility:
Design:
INCLUSION CRITERIA:
Age >= 6 and <= 70 years old
Germline mutation in the GATA binding protein 2 (GATA2) gene, predicted to be deleterious or previously reported in GATA2 deficiency as determined by targeted GATA2 sequencing performed at the National Institutes of Health (NIH)
Clinical manifestation(s) consistent with a diagnosis of GATA2 deficiency, including any of the following (Note: only one clinical manifestation is required):
"Early stage" GATA2 deficiency defined as a hypocellular for age bone marrow with less than 5% blasts and normal cytogenetics or favorable cytogenetics (defined as "good" or "very good" cytogenetics risk groups plus trisomy 8)
Availability of an 8/8 HLA-matched related or unrelated donor, a 7/8 HLA-matched unrelated donor or a haploidentical related donor
Lansky (for participants < 16 years of age) or Karnofsky (for participants >=16 years of age) performance status of >= 40%
Left ventricular ejection fraction > 40%, preferably by 2-D echocardiogram (echo) obtained within 90 days prior to treatment initiation
Participants must have adequate organ function as defined below:
Adult participants: <=2.0 mg/dl and creatinine clearance >= 30 ml/min.
Pediatric participants (<18 years old): creatinine <1.5 mg/dL and a creatinine clearance using the Schwartz Formula > 30 mL/min/1.73m^2
EXCLUSION CRITERIA: