Using Briquilimab to Improve Stem Cell Transplants for GATA2 Deficiency
A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency
This study is testing if a new treatment called Briquilimab can make stem cell transplants safer and more effective for people with GATA2 deficiency.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 6 Years to 70 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | chemotherapy, cyclophosphamide, fludarabine, Briquilimab |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT05907746 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and effectiveness of Briquilimab-based conditioning in allogeneic hematopoietic stem cell transplantation for patients with GATA2 deficiency. The study will involve participants aged 6 to 70 who have a confirmed GATA2 gene mutation and related clinical manifestations. Participants will undergo a series of screenings and tests, including physical exams and blood tests, before receiving the treatment through a central venous catheter. The primary goal is to determine if this new approach can enhance donor engraftment and reduce transplant-related complications.
Who should consider this trial
Good fit: Ideal candidates are individuals aged 6 to 70 with a confirmed GATA2 gene mutation and clinical manifestations of GATA2 deficiency.
Not a fit: Patients with advanced GATA2 deficiency or those without a suitable donor may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could make stem cell transplants safer and more effective for patients with GATA2 deficiency.
How similar studies have performed: Previous studies have shown promising results with hematopoietic stem cell transplantation for GATA2 deficiency, but the use of Briquilimab is a novel approach.
Eligibility criteria
Show full inclusion / exclusion criteria
* INCLUSION CRITERIA: * Age \>= 6 and \<= 70 years old * Germline mutation in the GATA2 gene, predicted to be deleterious or previously reported in GATA2 deficiency as determined by targeted GATA2 sequencing performed at the NIH * Clinical manifestation(s) consistent with a diagnosis of GATA2 deficiency, including any of the following (Note: only one clinical manifestation is required): * History of severe, disfiguring, and/or recurrent infections * Low monocyte (\< 190 cells/microL), B cell (\< 61 cells/microL) and/or NK cell (\< 126 cells/microL) counts * Myelodysplastic syndrome by World Health Organization (WHO) criteria * 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: * Total bilirubin \<=2.5 x upper limit of normal (ULN) * Alanine transaminase (ALT) and aspartate aminotransferase (AST) \<= 5 x ULN * Creatinine: 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 * Pulmonary function tests (PFT)s: FEV1 and adjusted DLCO \>30%. Children who are unable to cooperate for PFTs due to age are still eligible if no evidence of dyspnea at rest and no need for supplemental oxygen * Women of childbearing potential (WOCBP) and men must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, tubal ligation, partner has had the previous vasectomy) at the study entry, for the duration of study treatment, and for at least one-year post-allogeneic HCT or 12 months after completion of chemotherapy preparative administration if HCT is not performed for women and for 4 months for the same for men. * Breastfeeding participants must be willing to discontinue breastfeeding * Willingness to remain in the NIH hospital or, if discharged, stay close to the NIH (60 minutes drive), for a minimum of 100 days after transplant or longer if there are complications. The participants must commit to having an adult caregiver with them during the first 100 days after transplant in case of discharging from the hospital before 100 days verified by social worker * Participants with hepatitis B virus (HBV) or hepatitis C virus (HCV) antibody-positive testing are allowed if HBV DNA \<100 IU/m or HCV RNA level is undetectable. Additionally, transplantation must be approved by a hepatology consult for these participants * Participants or parents/guardians must be able to understand and willing to sign a written informed consent document EXCLUSION CRITERIA: * Participants with a Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score \>8 * Participants who have received any investigational agents within 4 weeks before treatment initiation with the exception of virus-specific T cells for the treatment of viral infection/reactivation prior to allogeneic HCT * Participants with a history of hematologic malignancy (e.g., AML, CMML). Note: participants with MDS are included * History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (fludarabine, cyclophosphamide, tacrolimus, mycophenolate mofetil, granulocyte-colony stimulating factor (G-CSF)) used in the study * Presence of active malignancy. Note: participants with malignancy driven by viruses (e.g., human papillomavirus (HPV) or HPV or Epstein-Barr virus (EBV)) are allowed as the immune reconstitution after transplant may control the malignancy and participants with MDS are allowed * Human immunodeficiency virus (HIV)-infected participants * Pregnancy (confirmed with Beta-HCG serum or urine pregnancy test performed in WOCBP at screening) * Uncontrolled intercurrent illness or social situations (as determined by social work consult) that would limit compliance with study requirements
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Danielle E Pregent-Arnold, M.D. — National Cancer Institute (NCI)
- Study coordinator: Lisa Duncan, R.N.
- Email: duncanl@mail.nih.gov
- Phone: (240) 858-7019
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.